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Permissive Hypotension
Barry Armstrong, 7:10, October 2002

Barry Armstrong
General Surgeon - Dryden, Ontario, Canada


Understanding permissive hypotension in trauma care

Permissive hypotension is a hot topic in trauma circles. In the late 20th century, the early care for an injured person included “2 large-bore Intravenous lines, running wide open”. The current trend, in ambulances and emergency rooms, is to limit fluid resuscitation, at least until hemorrhage is controlled -- by natural hemostasis, external pressure, angiography or surgery. Metaphorically, the tide of fluid resuscitation is ebbing; our bleeding patients are managed drier than previously.

Editorial - Permissive Hypotension
Ken Mattox

Trauma-List discussion of Permissive Hypotension in Trauma Resuscitation

To help you understand why the tide has turned, these references include abstracts, plus access to some full text articles. Text in blue gives a brief opinion about the reference.

If you have additions, corrections or comments please email Barry Armstrong or


Hypotensive resuscitation during active hemorrhage: Impact on in-hospital mortality

Dutton RP, MacKenzie CF, Scalea TM,
R Adams Cowley Shock Trauma Center, and the Departments of Anesthesiology and Surgery,
University of Maryland School of Medicine, Baltimore, Maryland.

J Trauma 2002 June;52(6):1141-1146

Background: Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP). One human trial has demonstrated improved survival when fluid resuscitation is restricted, whereas numerous laboratory studies have reported improved survival when resuscitation is directed to a lower than normal pressure. We hypothesized that fluid resuscitation titrated to a lower than normal SBP during the period of active hemorrhage would improve survival in trauma patients presenting to the hospital in hemorrhagic shock.

Methods: Patients presenting in hemorrhagic shock were randomized to one of two fluid resuscitation protocols: target SBP > 100 mm Hg (conventional) or target SBP of 70 mm Hg (low). Fluid therapy was titrated to this endpoint until definitive hemostasis was achieved. In-hospital mortality, injury severity, and probability of survival were determined for each patient.

Results: One hundred ten patients were enrolled over 20 months, 55 in each group. The study cohort had a mean age of 31 years, and consisted of 79% male patients and 51% penetrating trauma victims. There was a significant difference in SBP observed during the study period (114 mm Hg vs. 100 mm Hg, p < 0.001). Injury Severity Score (19.65 ± 11.8 vs. 23.64 ± 13.8, p = 0.11) and the duration of active hemorrhage (2.97 ± 1.75 hours vs. 2.57 ± 1.46 hours, p = 0.20) were not different between groups. Overall survival was 92.7%, with four deaths in each group.

Conclusion: Titration of initial fluid therapy to a lower than normal SBP during active hemorrhage did not affect mortality in this study. Reasons for the decreased overall mortality and the lack of differentiation between groups likely include improvements in diagnostic and therapeutic technology, the heterogeneous nature of human traumatic injuries, and the imprecision of SBP as a marker for tissue oxygen delivery.


Effects of delaying fluid resuscitation on an injury to the systemic arterial vasculature.

Holmes JF, Sakles JC, Lewis G, Wisner DH.
Division of Emergency Medicine, University of California, Davis, School of Medicine,
Sacramento, CA 95817-2282, USA.

Academic Emergency Medicine 2002 Apr;9(4):267-74.

OBJECTIVES: To determine the effects of delaying fluid on the rate of hemorrhage and hemodynamic parameters in an injury involving the arterial system.

METHODS: Twenty-one adult, anesthetized, sheep underwent left anterior thoracotomy and transection of the left internal mammary artery. A chest tube was inserted into the thoracic cavity to provide a continuous measurement of blood loss. The animals were randomly assigned to one of three resuscitation protocols: 1) no fluid resuscitation (NR), 2) standard fluid resuscitation (SR) begun 15 minutes after injury, or 3) delayed fluid resuscitation (DR) begun 30 minutes after injury. All of the animals in the two resuscitation groups received 60 mL/kg of lactated Ringer's solution over 30 minutes. Blood loss and hemodynamic parameters were measured throughout the experiment.

RESULTS: Total hemorrhage volume (mean SD) at the end of the experiment was significantly lower (p = 0.006) in the NR group (1,499 311 mL) than in the SR group (3,435 721 mL) or the DR group (2,839 1549 mL). Rate of hemorrhage followed changes in mean arterial pressure in all groups. Hemorrhage spontaneously ceased significantly sooner (p = 0.007) in the NR group (21 14 minutes) and the DR group (20 15 minutes) than in the SR group (54 4 minutes). In the DR group, after initial cessation of hemorrhage, hemorrhage recurred in five of six animals (83%) with initiation of fluid resuscitation. Maximum oxygen (O2) delivery in each group after injury was as follows: 101 34 mL O2/kg/min at 45 minutes in the DR group, 51 20 mL O2/kg/min at 30 minutes in the SR group, and 35 8 mL O2/kg/min at 60 minutes in the NR group.

CONCLUSIONS: Rates of hemorrhage from an arterial injury are related to changes in mean arterial pressure. In this animal model, early aggressive fluid resuscitation in penetrating thoracic trauma exacerbates total hemorrhage volume. Despite resumption of hemorrhage from the site of injury, delaying fluid resuscitation results in the best hemodynamic parameters.


Fluid resuscitation of the patient with major trauma

Fowler R, Pepe PE
University of Texas Southwestern Medical Center and
The Dallas Metropolitan Area Biotel (EMS) System,
Dallas, Texas, USA

Current Opinion in Anaesthesiology 2002 April;15:173-178

Current reviews and consensus documents now recommend a more discriminating approach to the traditional practices of delivering liberal infusions of intravenous fluid to all major trauma patients with suspected or known major hemorrhage. The evolving evidence suggests that aggressive fluid resuscitation prior to hemostasis leads to additional bleeding through hydraulic acceleration of hemorrhage, soft clot dissolution, and dilution of clotting factors.

Aggressive preoperative fluid infusion is still considered appropriate for unconscious patients without palpable blood pressure or for those with controllable hemorrhage (e.g. isolated extremity or head injury), However, the latest recommendations are to limit or delay intravenous fluid resuscitation preoperatively in those with uncontrollable hemorrhage (e.g. those with penetrating torso injuries), even if they are hypoperfusing.

Although most clinicians still generally support fluid resuscitation for multisystem blunt trauma, particularly with head injury, the most recent experimental data have begun to challenge this traditional practice as well, suggesting a ‘slow infusion’ approach when there is risk for uncontrolled internal bleeding. By providing oxygen delivery with slow, limited infusion, new hemoglobin-based oxygen carriers might help to resolve the current dilemma of having to limit preoperative resuscitation when there is risk of uncontrolled hemorrhage.


Matter for debate--Fluid resuscitation in pre-hospital trauma care: A consensus view

Greaves I, Porter KM, Revell MP
Selly Oak Hospital,
Birmingham, B29 6JD, UK

J.R.Coll.Surg.Edinb. 2002 April;47:2, 451-457


Fluid administration for trauma in the pre-hospital environment is a challenging and controversial area. There is, as yet no equivocal answer or view, which can be supported by clear, well-documented and reliable evidence. Nevertheless, a careful evaluation of what evidence is available does allow some provisional conclusions to be drawn. We believe that the following represent the best possible current expert consensus on pre-hospital fluids in trauma. As future evidence brings clarity to this area, these guidelines can be modified, and further consensus statements will be issued taking into account such information.

When treating trauma victims in the pre-hospital setting:

  • Cannulation should take place en route, where possible
  • Only two attempts at cannulation should be made
  • Transfer should not be delayed by attempts to obtain intravenous access
  • Entrapped patients require cannulation at the scene
  • Normal saline is recommended as a suitable fluid for administration to trauma patients
  • Boluses of 250 ml fluid may be titrated against the presence or absence of a radial pulse (caveats; penetrating torso injury, head injury, infants)

Prehospital fluid resuscitation of the patient with major trauma

Pepe PE, Mosesso Jr JV, Falk JL
University of Texas Southwestern Medical Center at Dallas,
Emergency Medicine, MC 8579, 5323 Harry Hines Boulevard, Dallas, TX 75390-8579, USA.

Prehospital Emergency Care 2002 Jan-Mar;6:81-91

The most appropriate prehospital approach to resuscitative fluid interventions for trauma patients involves: determining the mechanism of injury (i.e., blunt versus penetrating versus thermal injury); identifying anatomic involvement (i.e., truncal versus isolated head injury versus isolated extremity injury); and staging the condition (i.e., hemodynamic stability versus instability versus moribund state). Based on available data, the liberal use of fluid infusions for presumed uncontrolled internal hemorrhage, such as that usually occurring after penetrating abdominal and thoracic injuries, is no longer advised. Although some infusion might be appropriate in patients with extremely severe hemorrhage (i.e., no palpable blood pressure, unconscious), the priority in such patients is rapid evacuation to definitive surgical intervention, with airway control and intravenous access provided en route. The data are less clear for patients with blunt injuries, particularly those with closed head injury. Most researchers would still recommend that patients with isolated extremity and head injuries, either blunt or penetrating, are candidates for immediate support of blood pressure through fluid infusions. However, the addition of potential intra-abdominal, intrapelvic, or intrathoracic injuries with uncontrolled hemorrhage confounds the decision-making process. Although conventional wisdom has been to provide aggressive blood pressure support under these circumstances through judicious use of isotonic, or perhaps hypertonic, fluid resuscitation, recent experimental data challenge even this philosophy. Use of new blood substitutes might help to resolve some of these issues by providing oxygen delivery with limited volume in the face of uncontrolled hemorrhage.


Continuous fluid resuscitation and splenectomy for treatment of uncontrolled hemorrhagic shock after massive splenic injury

Abu-Hatoum O, Bashenko Y, Hirsh M, Krausz MM,
Department of General Surgery and the Laboratory for Shock and Trauma Research,
Rambam Medical Center, and the Bruce Rappaport Faculty of Medicine,
Technion-Israel Institute of Technology, Haifa, Israel.

J Trauma 2002 Feb;52:253-258

Background: Using a standardized massive splenic injury (MSI) model of uncontrolled hemorrhagic shock, we studied the effect of continuous fluid resuscitation and splenectomy on the hemodynamic response and survival in rats.

Methods: The animals were randomized into seven groups: group 1 (n = 8), sham-operated; group 2 (n = 8), MSI untreated; group 3 (n = 8), MSI treated with 7.5 mL/kg/h of 7.5% NaCl (hypertonic saline [HTS]) for 1 hour; group 4 (n = 8), MSI treated with 7.5 mL/kg/h hydroxyethyl starch (HES-7.5) for 1 hour; group 5 (n = 8) MSI treated with 35 mL/kg/h Ringer’s lactate (RL) solution (RL-35) for 1 hour; group 6 (n = 8) MSI treated with 70 mL/kg/h RL for 1 hour (RL-70); and group 7 (n = 8), MSI treated with 105 mL/kg/h RL for 1 hour (RL-105). In all MSI groups, splenectomy was performed 45 minutes after injury.

Results: MSI in untreated group 2 resulted in a fall of mean arterial pressure from 105.9 ± 10.7 mm Hg to 27.0 ± 6.7 mm Hg (p < 0.001) in 60 minutes. Mean survival time after splenectomy in this group was 160.7 ± 29.7 minutes, and total blood loss was 34.8 ± 4.7% of blood volume. Continuous HTS infusion with splenectomy in group 3 was followed by a total blood loss of 38.7 ± 4.4% and mean survival time was 176.5 ± 23.2 minutes. HES-7.5 infusion and splenectomy was followed by a total blood loss of 39.6 ± 2.5% and survival time was 171.6 ± 19.5 minutes. Continuous infusion of increasing volumes of RL in groups 5, 6, and 7 was followed by increase in blood loss to 29.0 ± 4.1%, 50.2 ± 3.1% (p < 0.001), and 62.7 ± 7.1% (p < 0.002) of total blood volume, respectively. Mean survival time in groups 5, 6, and 7 was 233.5 ± 6.5 minutes (p < 0.04), 207.6 ± 17.0 minutes (p < 0.05), and 158 ± 26 minutes, respectively.

Conclusion: Continuous infusion of large-volume RL and splenectomy after massive splenic injury resulted in a significant increase in intra-abdominal bleeding and shortened survival time compared with small-volume RL infusion.


Low-volume fluid resuscitation for presumed hemorrhagic shock: helpful or harmful?

Stern SA.
Department of Emergency Medicine,
University of Michigan, Ann Arbor, Michigan

Current Opinion in Critical Care. 2001 Dec;7(6):422-30.

For the past 4 decades, the standard approach to the trauma victim who is hypotensive from presumed hemorrhage has been to infuse large volumes of fluids as early and as rapidly as possible. The goals of this treatment strategy are rapid restoration of intravascular volume and vital signs towards normal, and maintenance of vital organ perfusion. The most recent laboratory studies and the only clinical trial evaluating the efficacy of these guidelines however, suggest that in the setting of uncontrolled hemorrhage, today's practice of aggressive fluid resuscitation may be harmful, resulting in increased hemorrhage volume and subsequently greater mortality. This has been demonstrated in animal models representative of penetrating trauma as well as those representative of blunt trauma. The data strongly suggest that limited or hypotensive resuscitation may be preferable for the trauma victim with the potential for ongoing uncontrolled hemorrhage. Limited resuscitation provides a mechanism of avoiding the detrimental effects associated with early aggressive resuscitation, while maintaining a level of tissue perfusion that although decreased from the normal physiologic range is adequate for short periods. Large randomized clinical trials are necessary to confirm this new laboratory data. Future research should focus on developing resuscitation methods that may actually enhance tissue perfusion during limited resuscitation and therefore offset its potential detrimental effects.


Crystalloid and colloid resuscitation of uncontrolled hemorrhagic shock following massive splenic injury.

Krausz MM, Bashenko Y, Hirsh M.

Department of General Surgery, Laboratory for Shock and Trauma Research,
Rambam Medical Center, Haifa, Israel.

Shock. 2001 Nov;16(5):383-8.

Using a standardized massive splenic injury (MSI) model of uncontrolled hemorrhagic shock we studied the effect of vigorous crystalloid or colloid fluid resuscitation on the hemodynamic response, and survival in rats. The value of massive fluid infusion in uncontrolled hemorrhagic shock following intra-abdominal solid organ injury is still controversial. The effect of crystalloid and colloid infusion was studied following massive splenic injury.

The animals were randomized into six groups: group 1 (n = 8) sham-operated, group 2 (n = 12) MSI untreated, group 3 (n = 10) MSI treated with 41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate, LVRL), group 4 (n = 14) MSI treated with 5 mL/kg 7.5% NaCl (hypertonic saline, HTS), group 5 (n = 10) MSI treated with 7.5 mL/kg hydroxyethyl starch (HES-7.5), and group 6 (n = 11) MSI treated with 15 mL/kg hydroxyethyl starch (HES-15).

Following MSI mean arterial pressure (MAP) in untreated group 2 decreased from 109.1+/-4.5 to 49.8+/-9.6 mmHg (P < 0.001) in 60 min. Mean survival time was 132.1 18.7 min, and total blood loss was 30.2+/-4.1% of blood volume. LVRL infusion resulted in an early rise in MAP from 59.7+/-7.3 to 90.0+/-11.3 mmHg (P < 0.01), which then rapidly dropped to 11.7+/-4.5 mmHg (P < 0.001) after 60 min. The mean survival time was 82.5+/-18.2 min (P < 0.01), and total blood loss was 53.7 2.9% (P < 0.01). Total blood loss following HTS infusion was 32.2 4.0% and survival time was 127.9+/-19.7 min. HES-7.5 infusion only moderately increased bleeding to 44.2+/-3.9% (P < 0.05), but mortality remained unchanged. HES-15 infusion resulted in an increase in blood loss to 47.8+/-7.1% (0.01), survival time dropped to 100.7+/-12.3 min (P < 0.05). Vigorous large volume infusion of Ringer's lactate or HES following MSI resulted in a significant increase in intra-abdominal bleeding and shortened survival time compared to untreated, small volume HTS, or HES-7.5-treated animals.

The hemodynamic response to crystalloid or colloid infusion in blunt abdominal trauma is primarily dependent on the severity of injury and the rate of fluid resuscitation.

Reviewer’s note:
Longest survival was in the group with no fluids, shortest survival with large volume infusion.


Permissive hypotension during primary resuscitation from trauma and shock

Kreimeier U, Prückner S, Peter K,

in Yearbook of Intensive Care and Emergency Medicine, 2001
ed.,Springer: 331-341


Advances in fluid resuscitation of hemorrhagic shock.

Tremblay LN, Rizoli SB, Brenneman FD.
Sunnybrook & Women's College Health Sciences Centre,
University of Toronto, Ont.

Canadian Journal of Surgery. 2001 Jun;44(3):172-9.

The optimal fluid for resuscitation in hemorrhagic shock would combine the volume expansion and oxygen-carrying capacity of blood without the need for cross-matching or the risk of disease transmission. Although the ideal fluid has yet to be discovered, current options are discussed in this review, including crystalloids, colloids, blood and blood substitutes. The future role of blood substitutes is not yet defined, but the potential advantages in trauma or elective surgery may prove to be enormous.


Irreversible shock is not irreversible: a new model of massive hemorrhage and resuscitation.

Healey MA, Samphire J, Hoyt DB, Liu F, Davis R, Loomis WH.
Department of Surgery, University of Saskatchewan,
Saskatoon, Saskatchewan, Canada.

J Trauma. 2001 May;50(5):826-34.

BACKGROUND: Existing shock models do not address the patient with massive hemorrhage (> 1 blood volume). Such patients often die from irreversible shock. This model simulates the clinical scenario of massive hemorrhage and resuscitation (MHR) to determine if irreversible shock can be reversed.

METHODS: Lewis rats were bled at a rate of 1 estimated blood volume (EBV) per hour for 2 hours with simultaneous infusion of resuscitation mixture (RM) consisting of red blood cells and crystalloid. Blood pressure was maintained at a mean arterial pressure (MAP) of 50 mm Hg during the 2 hours of hemorrhage. Hemorrhage was stopped and resuscitation continued for 1 hour until 6, 8, or 10 x EBV of RM was infused. Control animals were subjected to a traditional fixed pressure hemorrhage to MAP of 50 mm Hg for 2 hours followed by resuscitation to MAP > 90 mm Hg for 1 hour with crystalloid alone. Two-week survival was compared using a chi2 test.

RESULTS: Control animals (n = 13) were hemorrhaged 48% 5% of EBV and had a mortality rate of 23%. MHR animals had severity and duration of hypotension identical to that of controls but were hemorrhaged 214% 8% of EBV. Despite receiving 390 mL/kg of RM and a final hematocrit of 37%, 14 of 15 animals resuscitated with 6 x EBV died from "irreversible" shock (mortality, 93%; p < 0.001 vs. controls). When very large volumes of resuscitation were used, survival rates improved significantly. The 10 x EBV group received 120% of lost red blood cells and 530 mL/kg of crystalloid and had 64% survival at 2 weeks (p < 0.01 vs. 6 x EBV group).

CONCLUSION: This MHR model is much more lethal than a traditional severe hemorrhage model and reproduces the clinical picture of irreversible shock. This irreversible shock can be reversed with very large volumes of resuscitation.

Reviewer’s note:
The control group (rats) was bled down to a blood pressure of 50 mm Hg and maintained there for 2 hours. The other groups had continuing hemorrhage, while fluid infusion was given. After 2 hours, hemorrhage was controlled. The fluid resuscitation was given to the experimental animals, during bleeding and after resuscitation.

No fluids until bleeding stopped : 23% 2-week mortality.
Giving fluids to 6 X EBV : 93% 2-week mortality.
Giving fluids to 10 X EBV : 36% 2-week mortality.


Improved survival with early fluid resuscitation following hemorrhagic shock.

Santibanez-Gallerani AS, Barber AE, Williams SJ, ZhaoB S Y, Shires GT
Department of Surgery, University of Nevada School of Medicine, 2040 W. Charleston Boulevard, Suite 501,
Las Vegas, Nevada 89102, USA.

World Journal of Surgery. 2001 May;25(5):592-7.

Recent studies have questioned the benefits of early fluid resuscitation in hemorrhagic shock. The purpose of the current study is to evaluate the effects of early fluid resuscitation (HSE) (15 minutes), delayed fluid resuscitation (HSD) (60 minutes), and no fluid resuscitation (HSU) on cytokine levels, hepatic resting membrane potential (Em), renal function, and mortality. Eighty male Sprague-Dawley rats (350-450 g) were hemorrhaged 35% of their total blood volume and then received 40, 80, or 100 ml of crystalloid per kilogram as intravenous fluids (IVFs). The implementation of HSE resulted in stabilization of the Em (-29 mV), which was significantly different from that seen with HSD or HSU (-24 and -29 mV, respectively). The timing of resuscitation did not affect the elevation of tumor necrosis factor (TNFalpha) levels. The interleukin-6 (IL-6) levels for the HSE group were 81, 101, and 274 pg/ml for 40, 80, and 100 ml/kg, respectively. In contrast, HSD group IL-6 levels were 440, 566, and 632 pg/ml for 40, 80, and 100 ml/kg (p < 0.0001). IL-6 levels for the HSU group was 427 pg/ml, which was significantly different from that of the HSE group (p < 0.05). Urine output was present in 58% of the HSE rats but only 24% in the HSD rats and 0% of the HSU rats. Mortality was 11% for HSE, 58% for HSD, and 50% for HSU rats.

Despite the recent studies questioning the benefits of early fluid resuscitation, these data show marked improvement in hepatic stability, the presence of urine output, decreased IL-6 levels, and significantly lower mortality when IVFs were given early after hemorrhagic shock. Furthermore, excessive fluid resuscitation (100 ml/kg) resulted in an increased inflammatory cytokine level and mortality and may account for the controversy.


Fluid resuscitation for the trauma patient.

Nolan J.

Resuscitation 2001 Jan;48(1):57-69.

Attempts at prehospital fluid replacement should not delay the patient's transfer to hospital. Before bleeding has been stopped, a strategy of controlled fluid resuscitation should be adopted. Thus, the risk of organ ischaemia is balanced against the possibility of provoking more bleeding with fluids. Once haemorrhage is controlled, normovolaemia should be restored and fluid resuscitation targeted against conventional endpoints, the base deficit, and plasma lactate. Initially, the precise fluid used is probably not important, as long as an appropriate volume is given; anaemia is much better tolerated than hypovolaemia. Colloids vary substantially in their pharmacology and pharmacokinetics and the experimental findings from one cannot be extrapolated reliably to another. We still lack reliable data to prove that any of the colloids reduce mortality in trauma patients. In the presence of SIRS, hydroxyethyl starch may reduce capillary leak. Hypertonic saline solutions may have some benefit in patients with head injuries although this has yet to be proven beyond doubt. It is likely that one or more of the haemoglobin-based oxygen carriers currently under development will prove to be valuable in the treatment of the trauma patient.


Permissive Hypotension

Riley B

in Recent Advances in Anaesthesia and Analgesia 21.
ed. Adams AP & Cashman JN. Publ. Churchill Livingstone London 2000.


A randomised controlled trial of prehospital intravenous fluid replacement therapy in serious trauma.

Turner J, Nicholl J, Webber L, Cox H, Dixon S, Yates D.

Health Technology Assessment 2000 Nov;4(31):1-57.

Summary points: The initiation by paramedics of intravenous fluid replacement in injured patients at the accident scene is becoming a routine procedure although there is uncertainty surrounding this practice. This pragmatic randomised study involving 1309 patients compared the effects of two different fluid protocols: A: intravenous fluids administered at the incident scene; and B: fluids withheld until arrival at hospital. No significant differences in outcome were found between the two protocol groups; but protocol compliance was poor – 31% of group A and 20% of group B received prehospital fluids. This study does not support the idea that protocols recommending fluid administration do harm. But it is possible that either giving fluids early does no harm, or that the specific protocols used make little difference. In the absence of clear evidence, the authors suggest that Ambulance services should concentrate on avoiding unnecessary delays and speeding up transfer to definitive care in hospital rather than concentrate on their fluids protocols.


Permissive hypotension

U. Kreimeier, S. Prueckner, K. Peter,
Department of Anaesthesiology, Klinikum Grosshadern,
Ludwig-Maximilian University, Munich (D)

SchweizMedWochenschr [Swiss Medical Weekly] 2000 Oct 21;130: 1516-24

In trauma patients restoration of intravascular volume in an attempt to achieve normal systemic pressure faces the risk of increasing blood loss and thereby potentially affecting mortality. Due to the lack of controlled clinical trials in this field, the growing evidence that hypotensive resuscitation results in improved long-term survival mainly stems from experimental studies in animals. The main differences between concepts for the reduction of blood loss in systemic hypotension are between "deliberate hypotension" (synonym "controlled hypotension", used intraoperatively), "delayed resuscitation" (where the hypotensive period is intentionally prolonged until operative intervention) and "permissive hypotension" (where restrictive fluid therapy increases systemic pressure without reaching normotension). In this review the concept of "permissive hypotension" is delineated on the basis of macro- and microcirculatory changes secondary to hypovolaemia and low driving pressure, and the potential indications and limitations are discussed.


Timing and volume of fluid administration for patients with bleeding following trauma.

Kwan I, Bunn F, Roberts I,
WHO Pre-Hospital Trauma Care Steering Committee.
Department of Paediatric Epidemiology and Biostatistics,
Institute of Child Health, 30 Guilford Street, London, UK, WC1N 1EH.

Cochrane Database of Systematic Reviews. Last updated 2000 Sep 25.
Repeated in the Cochrane Library, Issue 3, 2002:

BACKGROUND: Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding.

OBJECTIVES: To assess the effects of early versus delayed, and larger versus smaller volume of fluid administration in trauma patients with bleeding.

SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, the specialised register of the Injuries Group, MEDLINE, EMBASE, the National Research Register and the Science Citation Index. We checked reference lists of identified articles and contacted authors and experts in the field.

SELECTION CRITERIA: Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded.

DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality.

MAIN RESULTS: We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration: Three trials reported mortality and two coagulation data. In the first trial (n=598) relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval of 1.00-1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9-4.5) and 4.3 (95% CI 1.74-6.9) seconds respectively. In the second trial (n=50) RR for death with early blood transfusion was 5.4 (95% CI 0.3-107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0-8.0) seconds. In the third trial (n=1309) RR for death with early fluid administration was 1.06 (95% CI 0.77-1.47). Larger versus smaller volume of fluid administration: Three trials reported mortality and one coagulation data. In the first trial (n=36) RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28-22.29). Prothrombin time and Partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid as compared to 13.9 and 35.1 seconds in the comparison group. In the second trial (n=99) RR for death with a high (100 mm Hg) compared to low (70 mm Hg) systolic blood pressure resuscitation target was 1.02 (95% CI 0.27-3.85). In the third trial (n=25) there were no deaths.

CONCLUSIONS: We found no evidence from randomised controlled trials to support early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.


The role of intravenous therapy in the pre-hospital trauma setting

Brown D.

Literature Review, 2000

Reviewer’s comments:
Briefly covers types of shock. Dscusses recent trends to restrict fluids until hemorrhage is controlled.
A good introduction to the science of fluid therapy for shock.


Fluid resuscitation in the initial management of post-traumatic shock: the concept of permissive hypotension.

Brett AS.

Clinical Intensive Care 2000 June;11(3):121-6.

Haemorrhage is one of the major causes of death with the first hours after trauma. The control of haemorrhage has been recognized as the single most important intervention in the management of the bleeding patient; a fact that was emphasized by WB Cannon in his seminal description of the management of missile victims on the Western Front. Cannon also identified the early correction of hypothermia, careful transportation, opiate analgesia, splintage, and appropriate dressings as measures, which might influence the evolution of shock in the first hours after wounding. Such measures remain essential features of trauma resuscitation in the 21st century. Of critical relevance to the subject of this review, Cannon warned that the infusion of salt solutions to elevate the blood pressure before a surgeon was in a position to control bleeding might accelerate haemorrhage. The aim of this narrative review is to present evidence from animal models and clinical studies, so that clinicians and other healthcare workers can make rational decisions regarding the goals for fluid resuscitation in the initial phase of the resuscitation of the bleeding trauma patient.


The effect of vigorous fluid resuscitation in uncontrolled hemorrhagic shock after massive splenic injury.

Solomonov E, Hirsh M, Yahiya A, Krausz MM.
Department of Surgery A, Rambam Medical Center, Haifa, Israel.

Critical Care Medicine. 2000 Mar;28(3):749-54.

Regardless of origin, uncontrolled hemorrhage is uncontrolled hemorrhage
Tisherman SA.
Critical Care Medicine. 2000 Mar;28(3):892-4

OBJECTIVE: Using a standardized massive splenic injury model of uncontrolled hemorrhagic shock, we studied the effect of vigorous fluid resuscitation on the hemodynamic response and survival time in rats. DESIGN: Randomized, controlled study. Duration of follow-up was 4 hrs.

SETTING: University research laboratory.

SUBJECTS: Adult male Sprague-Dawley rats, weighing 240-430 g.

INTERVENTIONS: Standardized massive splenic injury was induced by two transverse incisions in the rat's spleen. The animals were randomized into four groups: group 1 (n = 8) underwent sham operation; in group 2 (n = 15), massive splenic injury was untreated; in group 3 (n = 15), massive splenic injury was treated with 41.5 mL/kg 0.9% sodium chloride (large-volume normal saline); and in group 4 (n = 15), massive splenic injury was treated with 5 mL/kg 7.5% sodium chloride (hypertonic saline).

MEASUREMENTS AND MAIN RESULTS: The hemodynamic and metabolic variables in the sham-operated group 1 were stable throughout the experiment. Mean arterial pressure in group 2 decreased from 86.5 +/- 4.0 to 50.3 +/- 6.3 mm Hg (p < .001) in the first 15 mins after massive splenic injury. Mean survival time in group 2 was 127.5 +/- 17.0 mins; total blood loss was 33.8% +/-2.6% of blood volume; and the mortality rate at 1 hr was 13.3%. Bolus infusion of large-volume normal saline after 15 mins resulted in an early increase in mean arterial pressure from 48.6 +/-7.4 to 83.3 +/- 7.2 mm Hg (p < .01); it then rapidly decreased to 24.6 +/- 8.6 mm Hg (p < .001) after 60 mins. The mean survival time (95.3 +/- 16.4 mins) was significantly lower than in group 2 (p < .01); total blood loss (48.0% +/- 4.3%) was significantly higher than in group 2 (p < .01); and mortality rate in the first hour was 33.3% (p < .05). Bolus infusion of hypertonic saline also decreased survival time to 93.3 +/- 20.3 mins (p < .01), but total blood loss was 35.2% +/- 3.0%, which was not significantly different from the blood loss in group 2. The mortality rate in the first hour (60.0%) was significantly higher than in group 2 (p < .005).

CONCLUSIONS: Vigorous infusion of normal saline after massive splenic injury resulted in a significant increase in intra-abdominal bleeding and decreased survival time. The hemodynamic response to crystalloid infusion in blunt abdominal trauma is primarily dependent on the severity of injury and the rate of blood loss.


Crystalloid or colloid resuscitation of uncontrolled hemorrhagic shock after moderate splenic injury.

Krausz MM, Bashenko Y, Hirsh M.
Department of Surgery A, Rambam Medical Center, Haifa, Israel.

Shock. 2000 Mar;13(3):230-5.

Using a standardized moderate splenic injury (MSI) model of uncontrolled hemorrhagic shock, we studied the effect of vigorous crystalloid or colloid fluid resuscitation on the hemodynamic response and survival time in rats. The animals were randomized into 6 groups: group 1 (n = 8) sham-operated, group 2 (n = 10) MSI untreated, group 3 (n = 10) MSI treated with 41.5 mL/kg Ringer's lactate (large-volume Ringer's lactate [LVRL]), group 4 (n = 10) MSI treated with 5 mL/kg 7.5% NaCl (hypertonic saline [HTS]), group 5 (n = 10) MSI treated with 7.5 mL/kg hydroxyethyl starch (HES-7.5), group 6 (n = 10) MSI treated with 15 mL/kg hydroxyethyl starch (HES-15). After MSI, mean arterial pressure (MAP) in group 2 decreased from 105.0+/-5.6 to 64.0+/-12.7 mmHg (P < 0.001) after 60 min. Mean survival time was 157.4+/-28.9 min, and total blood loss was 24.0+/-5.4% of blood volume. LVRL infusion resulted in an early rise in MAP from 75.2+/-8.7 to 96.7+/-9.0 mmHg (P < 0.01), which then rapidly dropped to 43.0+/-9.7 mmHg (P < 0.001) after 60 min. The mean survival time was 140.7+/-22.3 min, and total blood loss was 41.4+/-4.8% (P < 0.05). Total blood loss following HTS infusion was 24.7+/-3.7%, and mean survival time was 177.5+/-18.9 min. HES-7.5 infusion was followed by bleeding of 25.6+/-5.1%, and mean survival time was 181+/-16.1. HES-15 infusion resulted in an increase in blood loss to 48.2+/-7.3% (P < 0.05), and mean survival time of 133.0+/-27.7 min.

Large-volume Ringer's lactate (LVRL) or hydroxyethyl starch (HES-15) infusion in uncontrolled hemorrhagic shock after moderate splenic injury resulted in a significant increase in intra-abdominal bleeding, but survival time remained unchanged compared with untreated, small-volume HTS-, or HES-7.5-treated animals. The hemodynamic response to large-volume crystalloid or colloid infusion was similar to moderate large-vessel injury.


Early changes in Oxygenation and Chest Wall Compliance associated with Large Volume Shock Resuscitation

Marvin RG, McKinley BA, Cocanour CS, Moore FA,
University of Texas-Houston Medical School, Houston, TX

Poster, AAST 2000

Conclusion: Patients who sustain major trauma and are resuscitated with large volumes of isotonic crystalloid solution have significant decreases in oxygenation and pulmonary compliance. However, both parameters start to improve within 48 hours. Sustained respiratory failure due only to the volume of fluid administered is unlikely.


Effects of traditional versus delayed resuscitation on serum lactate and base deficit.

Baron BJ, Sinert RH, Sinha AK, Buckley MC, Shaftan GW, Scalea TM.
Department of Emergency Medicine, SUNY Health Science Center at Brooklyn,
New York, NY 11203, USA.

Resuscitation. 1999 Dec;43(1):39-46.

OBJECTIVE: To test the hypothesis that delayed resuscitation of hemorrhagic shock produces a less severe shock insult than traditional resuscitation, characterized by repeated episodes of alternating hypotension and normotension.

METHODS: Female pigs were divided into three groups. Sham operated controls (C) (n = 4), sustained hypotension (SS) (n = 6), and hypotension with multiple cycles of shock and resuscitation (SR) (n = 6). SS and SR animals were bled to a mean arterial pressure (MAP) of 50 mmHg. SS animals were maintained at an MAP of 50 mmHg for 65 min and then resuscitated to baseline blood pressure with normal saline and shed blood. SR animals were initially bled and maintained at an MAP of 50 mmHg for 35 min, resuscitated to baseline BP, and subsequently bled and resuscitated twice more. The total period of shock was the same in both SS and SR.

RESULTS: Following hemorrhage, there was a significant increase in lactate and base deficit in SS as compared to C and SR.

CONCLUSION: Delayed resuscitation produces a more profound shock insult than traditional resuscitation.


Fluid replacement.

Nolan J.

British Medical Bulletin. 1999 Dec;55(4):821-43

Appropriate fluid replacement is an essential component of trauma patient resuscitation. Once haemorrhage is controlled, the restoration of normovolaemia is a priority. In the presence of uncontrolled haemorrhage, aggressive fluid resuscitation may be harmful. The crystalloid-colloid debate continues, but existing clinical practice is more likely to reflect local biases and dogma rather than evidence-based medicine. Colloids vary substantially in their pharmacology and pharmacokinetics and the experimental findings based on one colloid cannot be extrapolated reliably to another. In the initial stages of trauma patient resuscitation, the precise fluid used is probably not important, as long as an appropriate volume is given. Later, when the microcirculation is relatively leaky, there may be some advantages to colloids such as hydroxyethyl starch. Hypertonic saline solutions may have some benefit in patients with head injuries. A number of haemoglobin solutions are under development but one of the most promising of these solutions will eventually become routine therapy for trauma patient resuscitation. In the mean time, contrary to traditional teaching, recent data suggest that a restrictive strategy of red cell transfusion may improve outcome in some critically ill patients.


Limited resuscitation with hypertonic saline, hypertonic sodium acetate, and lactated Ringer's solutions in a model of uncontrolled hemorrhage from a vascular injury.

Doucet JJ, Hall RI.
Department of Surgery, Dalhousie University, Queen Elizabeth II Health Sciences Centre,
Halifax, Nova Scotia, Canada.

J Trauma. 1999 Nov;47(5):956-63.

BACKGROUND: Hypertonic sodium acetate-dextran solution (HAD) causes vasodilatation and buffers metabolic acidosis. In controlled hemorrhage models, HAD in small volumes increases cardiac output without increasing blood pressure, thus creating a "high flow-low pressure" state. The objective of this study was to determine whether limited resuscitation of uncontrolled hemorrhage with HAD solution improves gut perfusion as measured by intestinal mucosal tonometry.

METHODS: Three groups of 10 swine were bled 25 mL/kg by means of a femoral artery catheter to produce a mean blood pressure of 30 mm Hg. A 4-mm abdominal aortic laceration was then produced by pulling out a preimplanted wire loop. Groups were then randomly assigned to be resuscitated with either lactated Ringer's solution, a hypertonic saline-dextran solution or HAD solution sufficient to maintain a mean blood pressure of 45 mm Hg for 5 hours or until death. Outcomes were measured by survival, intraperitoneal blood loss, hemodynamic monitoring, and ileal mucosal tonometry.

RESULTS: HAD infusions caused transient worsening of hypotension and were associated with increased mortality (p = 0.038). Blood loss and volumes required for resuscitation were significantly increased in the lactated Ringer's solution group. HAD showed significant buffering effect against metabolic acidosis in arterial blood only, but intestinal ileal mucosal tonometry was not different among the groups.

CONCLUSION: HAD did not improve gut perfusion despite buffering the systemic acidosis of shock and caused increased mortality. Limited resuscitation with any of these solutions is associated with significant mucosal acidosis.


Treatments to support blood pressure increases bleeding and/or decreases survival in a rat model of closed head trauma combined with uncontrolled hemorrhage.

Talmor D, Merkind V, Artru AA, Shapiro O, Geva D, Roytblat L, Shapira Y.
Division of Anesthesiology, Ben-Gurion University of the Negev, Faculty of Health Sciences,
Soroka Medical Center, Beer Sheva, Israel.

Anesth Analg. 1999 Oct;89(4):950-6.

Hemorrhagic hypotension may aggravate the detrimental effects of head trauma on neurologic outcome. Our study examined whether using phenylephrine or large volumes of saline IV to increase mean arterial blood pressure (MAP) to 70, 80, or 90 mm Hg during the combination of head trauma and uncontrolled hemorrhage would improve neurologic outcome. Rats were assigned to one of 17 groups. In Groups 1-5, the variables were head trauma (yes/no), hemorrhage (yes/no), 0 or 3 mL saline per milliliter of blood lost, and no target MAP. In Groups 6-11, hemorrhage was or was not combined with head trauma, and large volumes of saline were given IV to achieve target MAPs of 70, 80, or 90 mm Hg. Groups 12-17 were similar to Groups 6-11 except that phenylephrine was used rather than saline to achieve target MAPs. Saline increased blood loss at 2 h to approximately 16 and 25 mL at a MAP of 80 and 90 mm Hg respectively, increased (worsened) the neurodeficit score but not cerebral edema at 24 h, and decreased survival rate at 2 and 24 h. Because phenylephrine was fatal for 62 of 63 rats, group mean values for blood loss, neurodeficit score, and brain tissue specific gravity could not be calculated. We conclude that supporting MAP with either phenylephrine or large volumes of saline worsened the neurodeficit score and/or survival and did not affect cerebral edema formation in our rat model of head trauma combined with hemorrhage.

IMPLICATIONS: The results of this study indicate that maintaining mean arterial blood pressure at 70, 80, or 90 mm Hg with either phenylephrine or large volumes of saline worsened the neurodeficit score and/or survival and did not affect cerebral edema formation in our rat model of head trauma combined with hemorrhage.


Aggravated uncontrolled hemorrhage induced by intravenous fluid administration
Article in Swedish

Riddez L, Hahn R.
Kirurgkliniken, Stockholm.

Lakartidningen. 1999 Sep 15;96(37):3893-4.

A model of uncontrolled haemorrhage where a 0.5 mm laceration is made in the porcine abdominal aorta has shown outcome to be impaired by conventional fluid therapy given to restore blood volume. Findings in recent studies where the difference in blood flow rates, proximal vs. distal to the site of vascular lesion, was used as a measure of bleeding suggest the adverse effect of fluid therapy to be strongly associated with re-bleeding after primary haemostasis has occurred. Optimal survival is dependent on a fluid infusion rate ensuring balance between the risk of re-bleeding and the beneficial effects of fluid therapy on oxygen consumption.


Logistics of parental fluids in battlefield resuscitation

Peace FJ; Lyons WS.
Division of Surgery, Walter Reed Army Institute of Research,
Washington, DC 20307 USA

Military Medicine, 1999 Sept; 164(9):653-5.

The paper discusses the substantial reduction in weight and volume of the fluids of resuscitation that is possible and desirable on the basis of sound physiology and the vast experience of the U.S. Army in four major wars in this century. We note the major shift in emphasis from massive colloid and whole blood in World War II and Korea to massive crystalloid and packed cells in Vietnam and the serious complications with which this was associated. These complications were edematous in nature and best known as the Da Nang lung, or adult respiratory distress syndrome, multiorgan dysfunction syndrome, and systemic inflammatory response syndrome. The advantage of colloid in reducing the weight and volume of resuscitation fluids in forward areas by 60% to 90%, as well as in avoiding the edematous complications of crystalloids, are emphasized.


Prehospital Fluid Administration for Thoracic Trauma

Hyde AJ, Graham TR,

Pre-Hospital Immediate Care, 1999 June ;3:99-101

Fluid administration is an established component of resuscitation in cases of trauma. Often this occurs as part of a set protocol, and little thought is given to the pathophysiology of the underlying injury. This approach is often beneficial, particularly in hypovolaemic patients, and in the majority of cases will be harmless. Unfortunately, there are certain instances, particularly with thoracic trauma, when such an indiscriminate policy can be detrimental and even fatal. This has recently brought into question the whole issue of fluid resuscitation, and the concept of “hypotensive resuscitation has been introduced. This relies on fluid resuscitation only to the point of critical organ perfusion, and not beyond. Unless specifically indicated, fluids may be withheld until assessment in the emergency room. This policy not only prevents the potential for disastrous consequences of over transfusion, but reduces time spent at scene, and therefore expedites transfer.


Initial Resuscitation.

Mattox KL, Brundage SI, Hirshberg A.

New Horiz 1999 Spring;7(1): 4-9.


Initial resuscitation volume in uncontrolled hemorrhage: effects on organ function.

Haizlip TM Jr, Poole GV, Falzon AL.
Department of Surgery, University of Mississippi Medical Center,
Jackson 39216, USA.

American Surgeon 1999 Mar;65(3):215-7.

Conventional resuscitation of hypovolemia due to hemorrhage has consisted of aggressive fluid administration. Recent studies have suggested that surgical control of bleeding before fluid resuscitation might improve early survival. The effects of limited resuscitation on organ function have not been assessed in these studies. We developed a model of moderate intraperitoneal hemorrhage designed to evaluate long-term end-organ function after various resuscitation protocols. Male Sprague-Dawley rats underwent ketamine anesthesia, followed by placement of femoral artery and vein lines. Intraperitoneal hemorrhage was induced by division of distal branches of the ileocolic artery and vein. After 5 minutes of bleeding, the animals were randomized to one of three resuscitation groups: Group 1 received no fluid resuscitation before surgical control of the hemorrhage; Group 2 received 0.5 mL of lactated Ringer's solution (LR) every 5 minutes for a mean arterial pressure (MAP) of less than 80 mm Hg; Group 3 received 2.0 mL of LR every 5 minutes for a MAP of less than 80 mm Hg. In all three groups, after 20 minutes, the bleeding was surgically controlled. All rats were then resuscitated with LR to a MAP of 80 mm Hg. The intravascular lines were removed, and the rats were allowed to recover from anesthesia and were returned to animal holding. On the 7th day, survivors were sacrificed, and their blood was assayed for hematocrit and serum levels of bilirubin, alanine aminotransferase, urea nitrogen, and creatinine. Kidneys, lungs, and liver were harvested for microscopic examination. Survival was lower in Group 2 than in the other groups (90%, 60%, and 100%, respectively; P = 0.04), but all deaths occurred within 3 hours of hemorrhage and were due to either hypovolemia or anesthetic complications. No histologic abnormalities were identified in the livers of the animals that survived, but pulmonary atelectasis and mild-to-moderate renal tubular necrosis were identified uniformly. No histologic differences could be discerned between the groups. Hematocrit and indices of liver and renal function were similar in all groups, and no animal developed organ dysfunction. In this model of moderate uncontrolled intraperitoneal hemorrhage, the volume of fluid resuscitation, or the absence of resuscitation, had an inconsistent effect of 7-day survival and did not influence function or histologic appearance of the liver, lungs, or kidneys 7 days after hemorrhage.


Limited volume resuscitation in penetrating thoracoabdominal trauma.

de Guzman E. Shankar MN. Mattox KL.
Trauma Services, Ben Taub General Hospital,
Houston, TX 77030, USA.

AACN Clinical Issues. 1999 Feb;10(1):61-8,.

Trauma is the leading cause of death in young adults. Development of trauma centers in urban settings including emergency medical services has contributed greatly to the improved quality of trauma patient care. Based on animal experiments performed 3 decades ago, the traditional management of hypovolemic hemorrhagic shock includes adequate circulatory volume with aggressive initial infusion of crystalloid solution. However, in several recent animal studies, investigators have found that aggressive treatment with fluids before control of bleeding results in a higher mortality rate, especially if blood pressure is elevated. This notion has been supported by findings in a recent prospective, randomized study involving patients with penetrating injuries to the torso. This article discusses briefly the pathophysiology of shock and hemostasis and the current literature on fluid resuscitation, with emphasis on limited volume resuscitation in patients with penetrating thoracoabdominal injuries.


Controlled resuscitation for uncontrolled hemorrhagic shock

Burris D; Rhee P; Kaufmann C; Pikoulis E; Austin B; Eror A; DeBraux S; Guzzi L; Leppaniemi A.
Department of Surgery, Uniformed Services University of the Health Sciences,
Bethesda, Maryland 20814-4799 USA.

J Trauma, 1999 Feb;46(2):216-23

OBJECTIVE: To test the hypothesis that controlled resuscitation can lead to improved survival in otherwise fatal uncontrolled hemorrhage.

METHODS: Uncontrolled hemorrhage was induced in 86 rats with a 25-gauge needle puncture to the infrarenal aorta. Resuscitation 5 minutes after injury was continued for 2 hours with lactated Ringer's solution (LR), 7.3% hypertonic saline in 6% hetastarch (HH), or no fluid (NF). Fluids infused at 2 mL x kg(-1) x min(-1) were turned on or off to maintain a mean arterial pressure (MAP) of 40, 80, or 100 mm Hg in six groups: NF, LR 40, LR 80, LR 100, HH 40, and HH 80. Blood loss was measured before and after 1 hour of resuscitation.

RESULTS: Survival was improved with fluids. Preresuscitation blood loss was similar in all groups. NF rats did not survive 4 hours. After 72 hours, LR 80 rats (80%) and HH 40 rats (67%) showed improved survival over NF rats (0%) (p < 0.05). Rebleeding increased with MAP. Attempts to restore normal MAP (LR 100) led to increased blood loss and mortality.

CONCLUSION: Controlled resuscitation leads to increased survival compared with no fluids or standard resuscitation. Fluid type affects results. Controlled fluid use should be considered when surgical care is not readily available


The effects of varying fluid volume and rate of resuscitation during uncontrolled hemorrhage.

Soucy DM, Rudé M, Hsia WC, Hagedorn FN, Illner H, Shires GT.
Department of Surgery, Texas Tech University Health Sciences Center,
Lubbock 79430, USA

J Trauma, 1999 Feb;46(2):209-15.

BACKGROUND: The role of rate and volume of infusion in survival from experimental uncontrolled hemorrhage was evaluated.

METHODS: Hemorrhage was initiated using tail resection in 43 female rats assigned to the following five groups: nonresuscitated; resuscitated with moderate volume, slower rate; resuscitated with moderate volume, faster rate; resuscitated with high volume, slower rate; and resuscitated with high volume, faster rate.

RESULTS: A trend toward improved survival was noted with faster rate of infusion (60 vs. 33.3% survival rate with moderate volume and 28.6 vs. 12.5% with high volume, compared with 16.7% in the nonresuscitated animals).

CONCLUSION: Rapid infusion of moderate volume of isotonic saline improved survival in uncontrolled hemorrhage. Extreme volumes, infused rapidly, also resulted in higher survival rates compared with those observed in nonresuscitated rats

Reviewer’s note:
This is evidence against ‘permissive hypotension’ for uncontrolled bleeding. This group published other studies that similarly show decreased mortality with fluid infusion (Surgery, 1998 and Annals of Surgery, 1995 – both in this list).


Early isotonic saline resuscitation from uncontrolled hemorrhage in rats.

Greene SP, Soucy DM, Song WC, Barber AE, Hagedorn FN, Illner HP, Shires GT.
Department of Emergency Medicine, Texas Tech University Health Sciences Center,
El Paso, USA.

Surgery. 1998 Sep;124(3):568-74

BACKGROUND: Attempts to modify traditional fluid resuscitation have been based on animal models that evaluate several variables including anesthesia. This study presents the effects of early saline resuscitation from severe uncontrolled hemorrhage unanesthetized rats.

METHODS: Sixty-three female Sprague-Dawley rats were equally divided into three groups: group A, nonresuscitated; and groups B and C, resuscitated with isotonic saline (40 and 80 mL/kg, respectively). Hemodynamics, blood loss, survival time, and mortality were recorded for 360 minutes after the hemorrhage, which was initiated by 75% resection of the tail.

RESULTS: In group C, 80 mL/kg of saline significantly lowered mortality (24% vs 76% and 71% for groups A and B, respectively) with concomitant increases in mean survival time (241 +/- 103 min vs 146 +/- 108 and 175 +/- 92 min for groups A and B, respectively). There were no statistically significant differences in blood loss, hematocrit, or hemodynamic parameters among the groups.

CONCLUSIONS: Early and adequate isotonic saline resuscitation of unanesthetized rats improved outcome despite continuing hemorrhage. The significantly lower mortality rate and increased survival time were not a result of transiently improved arterial pressure and did not correlate with blood loss. No significant bleeding increases were noted in the resuscitated groups.

Reviewer’s Note:
Like other studies by this group, this demonstrates improve survival with fluid infusion, in a rat experiment of uncontrolled bleeding. Their findings are opposite to those found by other researchers.


Delayed fluid resuscitation of head injury and uncontrolled hemorrhagic shock.

Bourguignon PR, Shackford SR, Shiffer C, Nichols P, Nees AV.
Department of Surgery, University of Vermont College of Medicine,
Burlington 05401, USA.

Archives of Surgery. 1998 Apr;133(4):390-8.

OBJECTIVE: To evaluate the effects of delayed vs early fluid resuscitation on cerebral hemodynamics after severe head injury and uncontrolled hemorrhagic shock.

DESIGN: Prospective, randomized, controlled experimental trial.

SETTING: Surgical research laboratory.

PARTICIPANTS: Immature swine (N=16) weighing 40 to 50 kg.

INTERVENTIONS: Twelve swine were subjected to cryogenic brain lesion and hemorrhage to maintain a mean arterial pressure (MAP) of 50 mm Hg. Animals were randomized to receive 1 L of Ringer lactate solution in 20 minutes, starting 20 minutes after injury and hemorrhage, followed by 1 L of Ringer lactate solution in 30 minutes (ER group) (n=6), or no fluid resuscitation (DR group) (n=6). The 4 control animals underwent instrumentation only. The study ended 70 minutes after head injury and hemorrhage.

MAIN OUTCOME MEASUREMENTS: Measurements of MAP, bilateral regional cerebral blood flow, serum hemoglobin level, systemic and regional cerebral oxygen delivery, and intracranial pressure performed at baseline and 20 (phase 1), 50 (phase 2), and 70 minutes (phase 3) after head injury and hemorrhage. Lesion size (percentage of ipsilateral cortex) was measured post mortem.

RESULTS: All animals survived the experimental period. Systemic cerebral oxygen delivery in the DR group was significantly lower at phase 3 compared with that of the ER group (31.5% vs 53.1% at baseline) (P=.03). However, bilateral regional cerebral oxygen delivery was significantly greater in the DR group at phase 3 compared with that of the ER group (71.5% vs 47.0% at baseline in the injured side; 72.9% vs 48.4% at baseline in the noninjured side) (P=.02). Bilateral cerebral blood flow was similar in all groups at all times. The ER group showed a trend toward a greater intracranial pressure elevation (6.8 vs -0.25) (P=.07) and lesion size (37.0% vs 28.6%) (P=.07). Hemoglobin level became significantly lower in the ER group at phase 2 (7.0 vs 10.7) (P=.03) and remained lower at phase 3 (6.9 vs 11.7) (P=.01).

CONCLUSIONS: Early fluid resuscitation with Ringer lactate solution following head injury and uncontrolled hemorrhagic shock worsens cerebral hemodynamics. Cerebral pressure autoregulation is sufficiently intact following head injury to maintain regional cerebral oxygen delivery without asanguineous fluid resuscitation.

Reviewer’s note:
They found that routine aggressive resuscitation (with Ringer's Lactate) in uncontrolled hemorrhage with severe head injury worsens cerebral hemodynamic parameter. Such fluid administration and could possibly contribute to secondary brain injury.


Resuscitation after uncontrolled venous hemorrhage: Does increased resuscitation volume improve regional perfusion?

Smail N, Wang P, Cioffi WG, Bland KI, Chaudry IH.
Center for Surgical Research and Department of Surgery,
Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.

J Trauma. 1998 Apr;44(4):701-8.

BACKGROUND: Recent studies have questioned the use of aggressive fluid resuscitation after uncontrolled arterial hemorrhage until the bleeding is controlled. However, it remains unknown whether resuscitation after hemorrhage from a venous origin (usually nonaccessible to surgical intervention) has any beneficial or deleterious effects on regional perfusion. The aim of this study, therefore, was to determine whether increased volume of fluid resuscitation after uncontrolled venous hemorrhage improves hemodynamic profile and regional perfusion in various tissues.

MATERIALS AND METHODS: After methoxyflurane anesthesia and midline laparotomy, both lumbar veins in the rat were severed, which resulted in lowering the mean arterial blood pressure to approximately 40 mm Hg. This pressure was maintained for 45 minutes by allowing further bleeding from the lumbar veins. The abdominal incision was then closed in layers and the animals received either 0, 10, or 30 mL of lactated Ringer's solution intravenously over a period of 60 minutes. Cardiac output and regional blood flow were determined by radioactive microspheres immediately or at 1.5 hours after the completion of resuscitation.

RESULTS: Fluid resuscitation with 10 or 30 mL lactated Ringer's solution increased mean arterial blood pressure and cardiac output immediately after resuscitation compared with the nonresuscitated animals. At both time points, regional perfusion in the heart, kidney and intestines remained significantly decreased compared with the sham values, irrespective of the volume of fluid resuscitation. Moreover, no further improvements in hemodynamics or regional perfusion occurred when volume resuscitation was increased from 10 mL to 30 mL. Total hepatic blood flow, however, increased with 10 mL lactated Ringer's solution compared with the other hemorrhage groups and the increase was evident even at 1.5 hours after resuscitation.

CONCLUSIONS: Fluid resuscitation after uncontrolled venous bleeding transiently increased cardiac output and mean arterial blood pressure compared with nonresuscitated animals. Moderate fluid administration, i.e., 10 mL, however, did increase total hepatic blood flow. In contrast, increasing the resuscitation volume to 30 mL did not improve hemodynamic parameters or regional perfusion. Thus moderate instead of no resuscitation or larger volume of resuscitation is recommended in an uncontrolled model of venous hemorrhage.


Central and regional hemodynamics during crystalloid fluid therapy after uncontrolled intra-abdominal bleeding.

Riddez L, Johnson L, Hahn RG.

J Trauma 1998 Mar;44:433-439

OBJECTIVE: To study the effect of graded crystalloid fluid resuscitation on central hemodynamics and outcome after intra-abdominal hemorrhage.

METHODS: Ten minutes after a 5-mm long laceration was produced in the infrarenal aorta, 32 pigs were randomized to receive either no fluid or Ringer's solution in the proportion 1:1, 2:1, or 3:1 to the expected amount of blood lost per hour (26 mL kg[-1]) over 2 hours. The hemodynamics were studied using arterial and pulmonary artery catheters and four blood flow probes placed over major blood vessels.

RESULTS: During the first 40 minutes after the injury, the respective blood flow rates in the distal aorta were 39% (no fluid), 41% (1:1), 56% (2:1), and 56% (3:1) of the baseline flow. Fluid resuscitation increased cardiac output but had no effect on arterial pressure, oxygen consumption, pH, or base excess. Rebleeding occurred only with the 2:1 and 3:1 fluid programs. Survival was highest with the 1:1 and 2:1 programs.

CONCLUSIONS: Crystalloid fluid therapy improved the hemodynamic status but increased the risk of rebleeding. Therefore, a moderate fluid program offered the best chance of survival Reviewer’s note: The authors wanted to test the "low fluid hypothesis" of transport. Limited volume resuscitation was more likely to result in survival than fluid therapy at the standard 3 litres given:1litre of lost blood ratio. (Then) standard resuscitation caused a higher bleeding rate.


Hypothermia from realistic fluid resuscitation in a model of hemorrhagic shock.

Silbergleit R, Satz W, Lee DC, McNamara RM.
Department of Emergency Medicine, George Washington University,
Washington, DC, USA.

Annals of Emergency Medicine 1998 Mar;31(3):339-43.

STUDY OBJECTIVE: To correlate changes in core body temperature with changes in mean arterial pressure (MAP) and cardiac output (CO) and with the administration of room-temperature intravenous fluids in a clinically relevant large-animal model of uncontrolled hemorrhage.

METHODS: Ten swine were subjected to uncontrolled hemorrhage through a flow-monitored shunt placed between the femoral artery and the peritoneal cavity. Animals were randomly assigned to a treatment or a control group. The control group (n=5) received no intravenous fluids. The treatment group (n=5) received 80 mL/kg (3:1 crystalloid/blood loss) ambient-temperature lactated Ringer's solution over a 10-minute resuscitation phase initiated 10 minutes after injury. CO and core body temperature, measured with the use of a pulmonary artery catheter, and MAP were the primary outcomes. We analyzed differences between groups with the use of repeated-measures ANOVA. Change of temperature was analyzed against the change in CO, and against fluid infusion for each interval, by means of regression analysis.

RESULTS: The unresuscitated control animals had no change in core temperature despite profound hemorrhagic shock and hypotension. The animals treated with fluids had a mean 2.6 degrees C decrease in core temperature during fluid resuscitation (95% confidence interval [CI], 1.8 to 3.5). A 1.5 degrees C decrease in core temperature (95% CI, .1 to 2.0) persisted at the end of 60 minutes (40 minutes after fluid resuscitation was discontinued). Core temperatures in control animals were 2.8 degrees C lower than those in treated animals after fluid resuscitation (95% CI, .8 to 4.8). Decreases in core temperature correlated with fluid infusion (beta=-35.2 mL/kg x degrees C, R2=.75) and increases in CO (beta=-1.46 L/min x degrees C, R2=.69).

CONCLUSION: Ambient-temperature crystalloid resuscitation in a clinically relevant large-animal model of hemorrhagic shock causes small decreases in core body temperature. Resuscitation rather than shock is the main cause of decreased body temperature in this model.


Reappraising the prehospital care of the patient with major trauma.

Pepe PE, Eckstein M.
Department of Emergency Medicine, Allegheny University of the Health Sciences,
Pittsburgh, Pennsylvania, USA.

Emerg Med Clin North Am. 1998 Feb;16(1):1-15.

Recent research efforts have demonstrated that many long-standing practices for the prehospital resuscitation of trauma patients may be inappropriate, particularly in certain circumstances. Traditional practices, such as application of antishock garments and IV fluid administration, may even be detrimental in certain patients with uncontrolled bleeding. Endotracheal intubation, although potentially capable of prolonging a patient's ability to tolerate circulatory arrest, may be harmful if overzealous ventilation further compromises cardiac output in such severe hemodynamic instability. If these procedures delay patient transport, any benefit they may offer could be outweighed by delaying definitive care. To improve current systems of trauma care, future trauma research must address the different mechanisms of injury, the anatomic areas involved, and the physiologic staging in a given patient.


Fluid resuscitation.

Myers C.
Department of Emergency Medicine, Royal Brisbane Hospital,
Queensland, Australia.

Eur J Emerg Med. 1997 Dec;4(4):224-32.

Contention over fluid resuscitation is not new. The issues however have changed considerably. The crystalloid/colloid debate has largely reached a stalemate with little to define clear differences between the two especially early in traumatic shock when increased capillary permeability is a minor issue. Blood, despite its difficulties and its cost is now safer than ever before and we will have to wait a number of years before routine use of blood substitutes becomes possible. Hypertonic saline and hypertonic saline dextran solutions used as an early bolus of 4-6 ml/kg and in conjunction with isotonic crystalloids and blood appear to be the new resuscitation fluids of first choice for haemorrhagic shock and there will be a progressive swing towards these fluids over the next 5 years. Application of the principles of minimal volume or delayed resuscitation requires the reconsideration of many entrenched attitudes and expectations present in the traditional management of haemorrhagic shock. Currently there is hard evidence to support its use only in ruptured AAA and penetrating truncal trauma but the application of the principles should be much more widespread. Minimal volume resuscitation emphasizes the need for urgent investigation and definitive management of uncontrollable haemorrhage reserving the early use of fluid resuscitation to maintain life only, until the integrity of the vascular circuit has been verified or restored. Thus it is the timing rather than the quantity of fluid which is the underlying issue. The questions which these new models of haemorrhage raise and the reconsideration of the physiology of haemorrhagic shock must be our focus. It would be foolish to replace the long-held dogma of aggressive fluid resuscitation in all situations with the new dogma of minimal volume resuscitation in all situations. Instead we must walk the tightrope attempting to understand the likely physiological mechanisms of our patients at an individual level. Fluid resuscitation has necessarily become more complex as the potential to do harm has been more clearly demonstrated. The use of resuscitation fluids must now receive as much care and consideration as is currently given to the prescription of potent drugs, weighing the potential benefits of a course of action against its possible side effects. Much research is required to clarify and refine the data on fluid resuscitation but there is little doubt that the conceptual changes which underlie this work on haemorrhagic shock offer the most exciting advances in fluid resuscitation seen in the past 30 years.


Restriction of fluid resuscitation in posttraumatic hypotension.

Tisherman SA, Peitzman AB.

Curr Opin Critical Care 1997;3(6):448-454.


Neurologic outcome with hemorrhagic hypotension after closed head trauma in rats: effect of early versus delayed conservative fluid therapy.

Feldman Z, Gurevitch B, Artru AA, Shapira Y, Reichenthal E.
Department of Neurosurgery, Soroka Medical Center, Faculty of Health Science, Ben-Gurion University,
Beer-Sheva, Israel.

J Trauma. 1997 Oct;43(4):667-72.

OBJECTIVE: This study examined (1) whether two previously reported, well-established models in rats, one a model of hemorrhagic hypotension and the other a model of closed head trauma, could be combined to evaluate neurologic outcome when hemorrhage occurs subsequent to head injury, and (2) the ability of the traditional, conservative approach to fluid therapy (3 mL of intravenous fluid for 1 mL of blood loss) to reverse the detrimental effects of hemorrhagic hypotension after closed head trauma. In addition, two strategies of fluid therapy (early and delayed) were examined.

METHODS: Fifty-six Sprague-Dawley male rats were divided into five groups with head injury at time 0 in groups 3 to 5, hemorrhage at 1 hour in groups 1, 2, 4, and 5, and intravenous fluid at 15 minutes (groups 2 and 5) or 60 minutes (groups 1 and 4) after hemorrhage. Head injury was delivered using a weight-drop impact of 0.5 J onto the closed cranium. Neurologic Severity Score (NSS) was determined at 1 hour (just before hemorrhage) and at 4 hours.

RESULTS: NSS at 1 hour did not differ between groups 3 to 5 (15.5 (9-24) to 16 (2-21), median (range)). The amount of bleeding did not differ between groups during the first 15 minutes of hemorrhage (2.8 0.8 to 3.7 2.0 mL, mean SD). After 60 minutes, cumulative blood loss in the delayed fluid therapy groups was less (3.1 1.13 mL in group 1 and 4.25 2.39 mL in group 4) than in the early fluid therapy groups (7.73 4.41 mL in group 2 and 6.85 2.36 mL in group 5) (analysis of variance, p < 0.01). The NSS of group 3 (head injury only) improved at 4 hours after injury (12 (5-20)), whereas the NSS of groups 4 and 5 (head injury followed by hemorrhage) deteriorated (24 (17-25) and 19.5 (9-25), respectively) (Kruskal-Wallis test,p < 0.05). In all the hemorrhage groups, fluid therapy failed to restore blood pressure to prehemorrhage levels.

CONCLUSION: It is concluded that the two individual models of hemorrhagic hypotension and closed head trauma in rats can be combined to evaluate outcome when hemorrhage occurs subsequent to head injury. Furthermore, traditional, conservative fluid therapy, whether early or delayed, failed to restore blood pressure or to improve NSS when hemorrhage occurred after head injury. Blood loss was greater with early fluid therapy whether or not head injury was present.


Ineffectiveness of On-Site Intravenous Lines: Is Prehospital Time the Culprit?

Sampalis JS. Tamim H. Denis R. Boukas S. Ruest SA. Nikolis A. Lavoie A. Fleiszer D. Brown R. Mulder D. Williams JI.
Department of Surgery, Trauma Programme, Montreal General Hospital, McGill University,
Quebec, Canada.

J Trauma 1997 Oct;43(4):608-617 (including discussion).

The purpose of the present study was to test the association between on-site intravenous fluid replacement and mortality in patients with severe trauma. The effect of prehospital time on this association was also evaluated. The design was that of an observational quasi-experimental study comparing 217 patients who had on-site intravenous fluid replacement (IV group) with an equal number of matched patients for whom this intervention was not performed (no-IV group). The patients were individually matched on their Prehospital Index obtained at the scene and were included in the study if they had an on-site Prehospital Index score > 3 and were transported alive to the hospital. The outcome measure of interest was mortality because of injury. The patients in the IV group had a significantly lower mean age (37 vs. 45 years; p < 0.001) and higher incidence of injuries to the head or neck (46 vs. 32%; p = 0.004), chest (34 vs. 17%; p < 0.001), and abdomen (28 vs. 12%; p < 0.001). The IV group also had a higher proportion of patients injured by motor vehicle crashes (41 vs. 27%; p = 0.003), firearms (9 vs. 2%; p = 0.001), and stabbing (20 vs. 9%; p = 0.001). The rate of extremity injuries (38 vs. 59%; p < 0.001) and falls (12 vs. 40%; p < 0.001) was lower for the IV group. In addition, the mean Injury Severity Score was significantly higher for the IV group (15 vs. 9; p < 0.001). The mortality rates for the IV and no-IV groups were 23 and 6% (p < 0.001). Logistic regression analysis showed that after adjusting for patient age, gender, Injury Severity Score, mechanism of injury, and prehospital time, the use of on-site intravenous fluid replacement was associated with a significant increase in the risk of mortality (adjusted odds ratio = 2.3; 95% confidence interval = 1.02-5.28; p = 0.04). To further evaluate the effect of prehospital time on the association between on-site IV use and mortality, the analysis was repeated separately for the following time strata: 0 to 30 minutes, 31 to 60 minutes, and >60 minutes. The adjusted odds ratios (95% confidence interval) for these strata were 1.05 (0.08-14.53; p = 0.97), 3.38 (0.84-13.62; p = 0.08), and 8.40 (1.27-54.69; p = 0.03). These results show that for prehospital times of less than 30 minutes, the use of on-site intravenous fluid replacement provides no benefit, and that for longer times, this intervention is associated with significant increases in the risk of mortality.

The results of this observational study have shown that the use of on-site intravenous fluid replacement is associated with an increase in mortality risk and that this association is exacerbated by, but is not solely the result of, increased prehospital times. Our findings are consistent with the hypothesis that early intravenous fluid replacement is harmful because it disrupts the normal physiologic response to severe bleeding. Although this evidence is against the implementation of on-site intravenous fluid replacement for severely injured patients, further studies including randomized controlled trials are required to provide a definitive answer to this question.


Timing of Trauma Resuscitation – Where on the spectrum should it occur?

Angood PB,

Trauma Quarterly 1997;13:251-261

Commentary – timing of trauma resuscitation

Bickell WH,

Trauma Quarterly 1997;13:267-268


Advances in Fluid Resuscitation

Dunn, R.,
The Canberra Hospital. Department of Emergency Medicine

Lecture notes on Emergency Medicine, August 31 1997


Central and regional hemodynamics during acute hypovolemia and volume substitution in volunteers.

Riddez L, Hahn R G, Brismar B, Strandberg Å, Svens‚n C, Hedenstierna G.
Stockholm, Sweden.

Critical Care Medicine 1997 April;25:635-640.

Objectives: To study the central and regional hemodynamics and oxygen consumption during acute hypovolemia and volume replacement with crystalloid and colloid solutions. Design: Prospective, randomized, laboratory investigation.

Setting: Clinical physiology department at a university hospital. Subjects: Eighteen healthy male volunteers, between 21 and 35 yrs of age (mean 26).

Interventions: Catheters were inserted in the cubital vein, brachial artery, pulmonary artery, thoracic aorta, right hepatic vein, and left renal vein for measurements of systemic arterial and pulmonary arterial pressures, total and central blood volumes, extravascular lung water, and the splanchnic (liver) and renal blood flow rates. The exchange of respiratory gases was measured, using the Douglas bag technique. Measurements were made before and after a venesection of 900 mL and again after the subjects had been randomized and received volume replacement with either 900 mL of Ringer's acetate solution 900 mL of albumin 5%, or 900 plus 900 mL of Ringer's solution.

Measurements and Main Results: Withdrawal of 900 mL of blood decreased cardiac output and the splanchnic and renal blood flow rates by between -16% and -20%. The oxygen uptake decreased by 13% in the whole body, while it remained unchanged in the liver and kidney. The systemic and pulmonary vascular resistances increased, while the extravascular lung water decreased. Autotransfusion of fluid from tissue to blood was indicated by hemodilution, which was most apparent in subjects showing only a minor change in peripheral resistance. Cardiac output, blood volume, and systemic vascular resistance were significantly more increased by infusion of 900 mL of albumin 5% than by 900 mL of Ringer's solution. However, infusion of 1800 mL of Ringer's solution increased the extravascular lung water and the pulmonary arterial pressures to significantly above baseline, while no significant difference from baseline was found after 900 mL of Ringer's acetate solution.

Conclusions: Withdrawal of 900 mL of blood induces similar reductions in cardiac output as in the splanchnic and renal blood flow rates. A fluid shift from the extravascular to the intravascular fluid compartment might restore up to 50% of the blood loss. Optimal volume substitution with Ringer's solution can be effectuated by infusing between 100% and 200% of the amount of blood lost.


Hypothermia and minimal fluid resuscitation increase survival after uncontrolled hemorrhagic shock in rats.

Kim SH, Stezoski SW, Safar P, Capone A, Tisherman S.
Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh Medical Center,
Pennsylvania 15260, USA

J Trauma. 1997 Feb; 42: 213-22.

OBJECTIVE: To test the hypothesis that protective-preservative moderate hypothermia during uncontrolled hemorrhagic shock (UHS) in rats increases survival.

DESIGN: Randomized outcome study in rats.

MATERIALS AND METHODS: UHS phase I of 90 minutes, with initial withdrawal of 3 mL/100 g of blood plus tail amputation, was followed by hemostasis and all-out resuscitation phase II from 90 to 150 minutes, and observation phase III to 72 hours. Forty male rats under light anesthesia and spontaneous breathing were randomized into four groups: Group 1 received no fluid resuscitation during UHS and normothermia (37.5 degrees C) throughout. Group 2 received no fluid resuscitation and hypothermia (30 degrees C) from 15 to 120 minutes. Group 3 received lactated Ringer's solution to maintain mean arterial pressure at 40 mm Hg during UHS and normothermia. Group 4 received lactated Ringer's solution to a mean arterial pressure of 40 mm Hg during UHS and hypothermia from 15 to 120 minutes.

RESULTS: UHS phase I was survived by 0 of 10 rats in group 1, 7 of 10 in group 2, 5 of 10 in group 3, and 10 of 10 in group 4 (p < 0.01 for group 1 vs. 2, 3, or 4; p <0.05 for group 4 vs. 3). Survival to 72 hours was achieved by 0 of 10 rats in group 1, 3 of 10 in group 2 (p < 0.001 vs. group 1), 1 of 10 in group 3, and 7 of 10 in group 4 (p < 0.001 vs. group 1, and p < 0.01 vs. group 3). All 72-hour survivors were neurologically normal. Necropsies in rats that died early during phase III showed edema and gastrointestinal hemorrhages.

CONCLUSIONS: Moderate hypothermia or limited (hypotensive) fluid resuscitation --best both combined—increases survival during and after UHS in rats.


Hypotensive resuscitation

Dries DH.

Shock 1996 Nov; 6:311-316

While the mechanism remains unclear, a growing body of experimental and clinical evidence suggests that aggressive crystalloid resuscitation in near fatal uncontrolled hemorrhage is associated with poor outcome. Limited attempts to restore blood pressure improve cardiac output, tissue perfusion, and survival while attempts to restore normal tension with crystalloid result in increased hemorrhage volume and higher mortality. The current standard of therapy for treatment of hemorrhagic shock includes initial aggressive crystalloid resuscitation. This mini-review summarizes some of the experimental and clinical data suggesting that this approach may not be desirable in the presence of uncontrolled hemorrhage following injury.


Effect of permissive hypotension in continuous uncontrolled intra-abdominal hemorrhage.

Silbergleit R, Satz W, McNamara RM, Lee DC, Schoffstall JM.
Medical College of Pennsylvania, Department of Emergency Medicine
Philadelphia 19129, USA.

Academic Emergency Medicine 1996 Oct;3(10):922-6.

OBJECTIVE: To determine the effects of aggressive fluid administration vs permissive hypotension on survival, blood loss, and hemodynamics in a model of uncontrolled hemorrhage in which bleeding has been shown to be continuous.

METHODS: In this porcine model, 10 animals were bled through a flow-monitored shunt placed between the femoral artery and the peritoneal cavity. The animals received either no fluid (n = 5) or 80 mL/kg lactated Ringer's solution (n = 5) during a resuscitation phase between 10 and 20 minutes postinjury, followed by a 40-minute evaluation phase. Arterial pressures, cardiac output (CO), and hemorrhage rate were measured. Survival and blood loss were calculated outcome measures.

RESULTS: The difference in survival between the animals left hypotensive (40%) and those receiving normotensive resuscitation (20%) was not significant (p = 0.49). In the animals receiving fluid resuscitation, mean arterial pressure (MAP) and CO increased during the resuscitative phase, but all the animals suffered the same pattern of hemodynamic deterioration in the evaluation phase. Rate of hemorrhage during the resuscitative phase was 20 +/- 5 mL/min in the animals not receiving fluid and 56 +/- 9 mL/min in the animals receiving fluids. Total blood loss was subsequently 20 mL/kg greater in the animals receiving fluids than in the animals without fluid resuscitation.

CONCLUSIONS: In this model of continuous uncontrolled hemorrhage, the difference in survival between the animals left hypotensive and the animals receiving fluid resuscitation was not statistically significant. Increases in MAP and CO with fluid resuscitation were transient and were offset by larger volumes of blood loss. In contrast to the aortotomy model (where thrombosis is likely and hypotensive resuscitation has proven beneficial), this model suggests that in continuous bleeding avoiding fluid resuscitation has a much smaller effect on outcome. Much of the benefit from hypotensive resuscitation may depend on having an injury that can stop bleeding.


Resuscitation of uncontrolled liver hemorrhage: effects on bleeding, oxygen delivery, and oxygen consumption.

Matsuoka T, Wisner DH.
Department of Surgery, University of California, Davis

J Trauma. 1996 Sep;41(3):439-45.

Using a standardized liver injury model of uncontrolled hemorrhage, we tested the effect of different fluid resuscitation regimens on hemodynamics, oxygen delivery, oxygen consumption, bleeding volume, and fluid resuscitation requirements. Rats were randomized into three bolus resuscitation groups 15 minutes after liver injury: lactated Ringer's solution (LR, n = 10), hypertonic saline (HS, n = 10), and hypertonic sodium acetate (HA, n = 10). In all resuscitation groups, a 4 mL/kg bolus was first infused at a rate of 0.4 mL/min. Continuous supplemental LR infusion was then given for 90 minutes to maintain a mean arterial pressure of 80 mm Hg. An initial bolus of LR led to minimal changes in hemodynamics. Initial resuscitation with HS markedly increased blood pressure and cardiac index. The bolus of HA increased cardiac index but did not increase blood pressure; systemic vascular resistance was significantly decreased and bleeding significantly increased. Resuscitation with HS did not increase bleeding compared with LR and resulted in the smallest total resuscitation volume requirement. Resuscitation with HS and HA both resulted in a rapid increase in oxygen consumption; LR did not increase oxygen consumption. Animals in the HS group had significantly higher oxygen extraction ratios at the conclusion of the experiment. The use of different bolus fluids for the resuscitation of uncontrolled hemorrhage resulted in significant differences in hemodynamics, oxygen metabolism, and blood loss even when subsequent resuscitation was the same in all groups. Results from large vessel injury animal models and clinical studies of patients with penetrating trauma may not apply to solid parenchymal injuries.


Fluid Resuscitation in a Model of Uncontrolled Hemorrhage: Too Much Too Early, or Too Little Too Late?

Leppaniemi A. Soltero R. Burris D. Pikoulis E. Waasdorp C. Ratigan J. Hufnagel H. Malcolm D.
Department of Surgery, Uniformed Services University of Health Sciences,
Bethesda, MD 20814-4799, USA.

Journal of Surgical Research 1996 July; 63: 413-418.

Early fluid resuscitation in hypotensive trauma patients is controversial due to the risk of increasing blood loss and mortality. We determined the effects of infusion rate and time of resuscitation on blood loss and mortality and compared the outcome to nonresuscitated animals in severe, uncontrolled hemorrhagic shock in a rat model. In anesthetized rats, piercing of the infrarenal aorta with a 25-G needle caused a fall of mean arterial pressure to <20 mm Hg and blood loss of about 20 ml/kg in 90% of the animals. Animals were assigned to the following treatment groups (n = 6): 60 ml/kg of lactated Ringer's solution (LR) infused at a rate of 1.5 ml/min and given at 2.5 min (Group I), 5 min (Group II), or 10 min (Group III) postinjury, or LR infused at a rate of 3.0 ml/min and given at 5 min (Group IV) or 10 min (Group V) postinjury. Another group (n = 9) was not resuscitated. The animals were followed for 3 hr. Total blood loss in Group I (30.5 +/- 2.6 ml/kg) was significantly (P < 0.05) higher when compared to nonresuscitated animals (22.1 +/- 0.8 ml/ kg) or Group III (22.7 +/- 1.0 ml/kg), and also significantly higher in Group IV (35.8 +/- 4.1 ml/kg) when compared to nonresuscitated animals or Group V (23.0 +/- 1.2 ml/kg). The mortality rate was 7/9 in nonresuscitated animals and 5/6 in Group IV, both were significantly higher than in Groups II, III, and V (0 or 1/6) and markedly higher than in Group I (2/6).

Conclusions: In this model of uncontrolled hemorrhage, initially uncorrected severe shock resulted in a high mortality rate. The risk of increased blood loss and mortality associated with early fluid resuscitation could be diminished by avoiding too fast of infusion rates early after the injury.


Uncontrolled Hemorrhage from Parenchymal Injury: Is Resuscitation Helpful?

Matsuoka T, Hildreth J, and Wisner DH.
Department of Surgery, University of California, Davis

J Trauma 1996 June; 40 (6): 915-922.

Fluid resuscitation increases blood pressure and may increase hemorrhage. We tested this hypothesis in a model of liver injury. After standardized injury, rats were randomized into four groups: no resuscitation (NR, n = 30), small volume lactated Ringer's solution (SVLR, 4 mL/kg, n = 30), large volume lactated Ringer's solution (LVLR, 24 mL/kg, n = 30), and hypertonic saline (HS, 4 mL/kg, n = 30). Terminal circulating volume was estimated using controlled hemorrhage experiments. Survival times and mortality rates were significantly lower in HS animals (10%) than in NR (50%) or SVLR (47%) animals. Blood pressure was significantly higher after HS, and this difference was sustained. Intraperitoneal blood volume was significantly higher with HS (26.0 +/- 0.7 mL/kg) and LVLR (26.9 +/- 0.6 mL/kg) compared with NR (21.5 +/- 0.7 mL/kg) and SVLR (22.5 mL/kg). Estimated terminal blood volume was significantly decreased in LVLR (29.3 +/- 0.6 mL/kg) compared with NR (33.3 +/- 0.7 mL/kg), SVLR (33.7 +/- 0.8 mL/kg), and HS (31.7 +/- 0.7 mL/kg).

CONCLUSION: Vigorous resuscitation increased bleeding from solid viscus injury. Small volume HS improves blood pressure and survival compared with no resuscitation. Results of large vessel hemorrhage models may not apply to parenchymal viscus injury.


Effects of isotonic saline solution resuscitation on blood coagulation in uncontrolled hemorrhage.

Selby JB, Mathis JE, Berry CF, Hagedorn FN, Illner HP, Shires GT.
Department of Surgery, Texas Tech University Health Sciences Center,
Lubbock 79430, USA.

Surgery. 1996 May;119(5):528-33.

BACKGROUND: It has been suggested that fluid resuscitation before surgical control of hemorrhage may lead to increased bleeding because of the elevated blood pressures and clotting factor dilution. This study was designed to assess the effects of isotonic saline solution resuscitation on blood coagulation during uncontrolled hemorrhage.

METHODS: Twenty-four female Sprague-Dawley rats were randomized into four groups with different resuscitation regimens: group A, no resuscitation; group B, 40 ml/kg in 4 minutes; group C, 80 ml/kg in 4 minutes; and group D, 80 ml/kg in 1 minute. Baseline blood samples were collected just before a sharp resection of 75% of the tail to initiate the hemorrhage; 15 minutes later the resuscitation began. Additional blood samples were obtained at 60 minutes after resection. The blood was analyzed for platelets, fibrinogen, prothrombin time, and activated partial thromboplastin time.

RESULTS: The largest differences between time 0 and 60 minutes were observed in group D with platelets decreasing 43.36% 7.86%, fibrinogen decreasing 57.10% 16.88%, and prothrombin time increasing from an average 16.5 to 19.2 seconds. These differences were statistically significant (p <0.05) with the Student's test.

CONCLUSIONS: The results suggested that even though the volume of resuscitation fluid did not appear to affect clotting time when compared with that of nonresuscitated animals, the rate of extremely large volume infusions may play an important role in the cessation of bleeding and consequently in the management of uncontrolled hemorrhagic shock.


Small-volume resuscitation restores hemorrhage-induced microcirculatory disorders in rat pancreas.

Vollmar MD, Preissler G, Menger MD.
Institute for Clinical and Experimental Surgery, University of Saarland, Germany.

Critical Care Medicine 1996 Mar;24(3):445-50.

OBJECTIVES: Pancreatic hypoxia/ischemia, as a consequence of shock-induced microcirculatory failure, is considered a causative factor in the initiation and/or progression of pancreatic tissue injury. The aim of this study was to compare the effects of "small volume resuscitation" with conventional isovolemic colloid and hypervolemic crystalloid resuscitation on pancreatic microcirculation after hemorrhagic shock. DESIGN: Randomized, controlled intervention trial.

SETTING: University laboratory.

SUBJECTS: Twenty-three male Sprague-Dawley rats anesthetized with á-chloralose mechanically and ventilated. Interventions: Rats subjected to 1 hr of hemorrhagic shock (mean arterial pressure of 40 mm Hg) were resuscitated with lactated Ringer's solution (four-fold shed volume/20 mins), 10% hydroxyethyl starch (shed volume/5 mins), or 7.2% sodium chloride-10% hydroxyethyl starch (10% shed volume/2 mins).

MEASUREMENTS AND MAIN RESULTS: The microcirculation of pancreatic acinar tissue was studied by means of intravital fluorescence microscopy and laser Doppler flowmetry. At 1 hr after resuscitation, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux were found to be significantly increased when compared with those values in the shock state. However, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux did not completely return to preshock values, regardless of the type of fluid used for resuscitation. At 15 mins and 1 hr after resuscitation, shock-induced capillary perfusion failure (reduction of functional capillary density) was restored to 91% to 94% of baseline values in all groups. Pancreatic capillary narrowing, indicating microvascular endothelial cell swelling, was abolished by resuscitation with both isotonic hydroxyethyl starch and hypertonic hydroxyethyl starch (p<.05 vs. lactated Ringer's solution).

CONCLUSIONS: Despite replacement of only 10% of actual blood loss, small-volume resuscitation with hypertonic hydroxyethyl starch is as effective as the ten-fold volume of isotonic hydroxyethyl starch and, due to prevention of microvascular endothelial cell swelling, superior to the 40-fold volume of isotonic lactated Ringer's solution in regard to restoration of the shock-induced microcirculatory disturbances of rat pancreatic acinar tissue.


Resuscitation from severe hemorrhage.

Shoemaker WC, Peitzman AB, Bellamy R, Bellomo R, Bruttig SP, Capone A, Dubick M, Kramer GC, McKenzie JE, Pepe PE, Safar P, Schlichtig R, Severinghaus JW, Tisherman SA, Wiklund L.
Department of Emergency Medicine, King/Drew Medical Center,
Los Angeles, CA 90059, USA.

Critical Care Medicine 1996 Feb;24(2 Suppl):S12-23

The potential to be successfully resuscitated from severe traumatic hemorrhagic shock is not only limited by the "golden 1 hr", but also by the "brass (or platinum) 10 mins" for combat casualties and civilian trauma victims with traumatic exsanguination. One research challenge is to determine how best to prevent cardiac arrest during severe hemorrhage, before control of bleeding is possible. Another research challenge is to determine the critical limits of, and optimal treatments for, protracted hemorrhagic hypotension, in order to prevent "delayed" multiple organ failure after hemostasis and all-out resuscitation. Animal research is shifting from the use of unrealistic, pressure-controlled, hemorrhagic shock models and partially realistic, volume-controlled hemorrhagic shock models to more realistic, uncontrolled hemorrhagic shock outcome models. Animal outcome models of combined trauma and shock are needed; a challenge is to find a humane and clinically realistic long-term method for analgesia that does not interfere with cardiovascular responses. Clinical potentials in need of research are shifting from normotensive to hypotensive (limited) fluid resuscitation with plasma substitutes. Topics include optimal temperature, fluid composition, analgesia, and pharmacotherapy. Hypotensive fluid resuscitation in uncontrolled hemorrhagic shock with the addition of moderate resuscitative (28 degrees to 32 degrees C) hypothermia looks promising in the laboratory. Regarding the composition of the resuscitation fluid, despite encouraging results with new preparations of stroma-free hemoglobin and hypertonic salt solutions with colloid, searches for the optimal combination of oxygen-carrying blood substitute, colloid, and electrolyte solution for limited fluid resuscitation with the smallest volume should continue. For titrating treatment of shock, blood lactate concentrations are of questionable value although metabolic acidemia seems helpful for prognostication. Development of devices for early noninvasive monitoring of multiple parameters in the field is indicated. Molecular research applies more to protracted hypovolemic shock followed by the systemic inflammatory response syndrome or septic shock, which were not the major topics of this discussion.


Fluid resuscitation of the trauma patient: how much is enough?

Hamilton SM; Breakey P. From the
Department of Surgery, University of Alberta Hospitals, University of Alberta,
Edmonton, Alta.

Canadian Journal of Surgery, 1996 Feb; 39(1): 11-16

Patient management in the prehospital resuscitative phase after trauma is vitally important to the outcome. Early definitive care remains the essential element in improving morbidity and mortality. In Canada, where a large proportion of trauma occurs at sites distant from a trauma centre, the prehospital resuscitative phase is long and has even greater potential to affect outcome. Conventional teaching about the end points of resuscitation has promoted the concept of normalization of hemodynamic parameters with maintenance of end-organ perfusion, as measured by the hourly urine output. Recent work in patients with a closed head injury and in patients with penetrating torso trauma challenge the notion that trauma patients are homogeneous with respect to these end points. In the Canadian setting of blunt injury, where a closed head injury is usually suspected and often present, the evidence from clinical studies suggests that an aggressive approach to maintaining blood pressure is warranted. In penetrating torso injury in an urban setting, there is evidence to suggest that delaying resuscitation until hemorrhage is controlled is beneficial. More Canadian clinical trials are required in this area. In the meantime, the priorities of resuscitation must be carefully assessed for each patient and pattern of injury.


Limiting Initial Resuscitation of Uncontrolled Hemorrhage Reduces Internal Bleeding and Subsequent Volume Requirements

Owens TH, Watson WC, Prough DS, Uchida T, Kramer GC
Department of Anesthesiology, University of Texas Medical Branch,
Galveston 77555-0591, USA.

J Trauma August 1995, 39(2):200-209 (including discussion)

We tested the hypothesis that full or "standard resuscitation" (SR) with Lactated Ringer's solution (LRS) results in increased bleeding in uncontrolled hemorrhagic shock, compared with a "limited prehospital resuscitation" (LPR) regimen and a control group of "no resuscitation" (NR). Cardiac output was used as physiological endpoint for resuscitation. Twenty swine had 25 mL/kg of blood withdrawn during a 30-minute controlled hemorrhage, followed by a 20-minute "prehospital" resuscitation regimen was conducted in three groups: the SR group (n = 6), LRS infused as needed to restore cardiac index (CI) to 100% baseline; the LPR group (n = 8), with resuscitation using LRS to 60% of baseline CI, with volume limited to 10 mL/kg; and the NR group (n = 6). After aortotomy repair, intraoperative resuscitation was continued for 120 minutes using LRS to achieve and maintain 80% of baseline mean arterial pressure. Blood pressure and cardiac index were greatly reduced, to 34% and 39% of baseline, respectively, by hemorrhage. During prehospital resuscitation, the SR group required 48.8 +/- 6.5 mL/kg of LRS, whereas the LPR group received 9.4 +/- 0.6 mL/kg (p < 0.05). Mean arterial pressure increased in all three groups during prehospital resuscitation (p < 0.05). Pulse pressures increased in the SR and LPR groups only (p < 0.05). The increment in oxygen delivery was significantly greater in the SR group, compared with the LPR group (p < 0.05), which in turn was significantly greater than the NR group (p < 0.05). Peritoneal blood volume was significantly higher in the SR group (20.6 +/- 5.6 mL/kg), versus the LPR (7.3 +/- 1.3 mL/kg; p < 0.05) and NR groups (3.0 +/- 0.9 mL/kg; p < 0.05). Crystalloid and whole blood requirements during the intraoperative resuscitation phase were significantly higher in the SR group (193 +/- 16.0 and 9.0 +/- 2.5 mL/kg), than in LPR (111.8 +/- 15.6 and 4.5 +/- 1.8 mL/kg; p < 0.05) and NR groups (128.5 +/- 32.3 and 3.9 +/- 2.3 mL/kg; p < 0.05). In the presence of uncontrolled hemorrhagic shock, LPR and NR can significantly reduce internal hemorrhage and subsequent intraoperative crystalloid and blood requirements.

Reviewer’s Note:
20 pigs, with aortotomy- induced uncontrolled haemorrhage. They compared pre-operative fluid trategies of ‘standard’ vs. ‘limited’ fluids vs. ‘no resuscitation’. Total blood lost was highest with standard fluid resuscitation, and least with no pre-operative fluid resuscitation.


Isotonic saline resuscitation in uncontrolled hemorrhage under various anesthetic conditions

Soucy DM, Sindlinger JF, Greene SP, Barber AE, Illner HP, Shires GT.
Department of Surgery, Texas Tech University Health Sciences Center, Lubbock. USA

Annals of Surgery, 1995 July; 222(1):87-93

OBJECTIVE: The authors evaluated the effect of early fluid resuscitation with isotonic saline (NaCl, 0.9%) on uncontrolled hemorrhage in rats under different anesthetic conditions.

SUMMARY/BACKGROUND DATA: Recently, it has been suggested that administration of fluids to patients during uncontrolled hemorrhage may produce adverse effects, and a postponement of resuscitation until surgical control of bleeding was recommended. Past clinical trials were inconclusive, and the results of recent experimental studies were affected by use of vasoactive anesthetics.

METHODS: One hundred thirty-five female Sprague-Dawley rats were randomly divided into three groups: group 1--unanesthetized; group 2—anesthetized with sodium pentobarbital; and group 3--anesthetized with a mixture of droperidol and ketamine. Uncontrolled hemorrhage was initiated with a 75% tail resection, and each group was further subdivided into three subgroups for the following treatment: (A) no resuscitation; (B) 40 mL/kg of isotonic saline; or (C) 80 mL/kg of isotonic saline, administered 15 minutes after the initiation of hemorrhage. Blood loss volume and survival time were recorded, and animals were observed up to 360 minutes.

RESULTS: At 6 hours, nonresuscitated animals of all groups exhibited the highest mortality rates (93%, 73%, 100% in groups 1, 2, and 3, respectively). Resuscitation significantly improved the survival; lowest mortality rates were observed after resuscitation with 80 mL/kg in groups 1 and 3 (33%) and 40 mL/kg in group 2 (40%). Fluid infusion increased hemorrhage rates in all anesthetized rats. No such increases in bleeding were observed in group 1.

CONCLUSIONS: Resuscitation with isotonic saline improved mortality in uncontrolled hemorrhage, even with concomitant increases in hemorrhage rates, under all three anesthetic conditions tested. Unanesthetized rats bled less than the animals under anesthesia and did not exhibit an increased blood loss in response to fluid infusion. Reviewer’s Note: This is evidence against ‘permissive hypotension’ in uncontrolled hemorrage. Fluid infusion improved mortality in bleeding animals, unlike most studies. The experimental animals were observed only 6 hours, or less.


Uncontrolled hemorrhagic shock outcome model in rats.

Capone A, Safar P, Stezoski SW, Peitzman A, Tisherman S.
Department of Surgery, Safar Center for Resuscitation Research (SCRR),
University of Pittsburgh Medical Center, PA 15260, USA.

Resuscitation. 1995 Apr;29(2):143-52.

During uncontrolled hemorrhagic shock (UHS) in acute animals models, attempts to achieve normotension with i.v. fluid resuscitation (FR) caused further bleeding and higher acute mortality. In the absence of a published clinically realistic long-term animal outcome study of UHS, we developed such a model in rats. In the preliminary study, phase I of the model involved 60 min of simulated 'pre-hospital' UHS by tail amputation and different FR regimens. Phase II involved 120 min of simulated 'hospital' treatment with hemostasis and all-out FR, including blood infusion. Phase III involved observing recovery and survival to 72 h (3 days). Rats were maintained under very light N2O-O2-halothane anesthesia and spontaneous breathing via mask during phases I and II and were awake during phase III. Tail amputation-induced UHS alone, studied in 4 groups of 10 rats each, resulted in unpredictable spontaneous hemostasis and great variability in shed blood volume, severity of shock, and mortality. The final model, which achieved consistent blood loss and outcome, included an initial volume-controlled hemorrhage of 3 ml/100 g over 15 min and untreated HS for another 15 min, followed by tail amputation for UHS over another 60 min. This phase I of 90 min was followed by phase II of 60 min. In group 1, without FR in phases I and II, all 10 rats died by 12 h. In group 2, without FR in phase I and hemostasis plus all-out FR with lactated Ringer's solution and blood to hematocrit (Hct) 30% in phase II, 5 of 10 rats died at the end of phase I and 9 of 10 died at the end of phase III. This final volume-initiated UHS model may be suitable for comparing different pre-hospital treatment modalities in terms of outcome.


Multiple Resuscitation Regimens in a Near-Fatal Porcine Aortic Injury Hemorrhage Model

Stern SA. Dronen SC. Wang X.
Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Academic Emergency Medicine 1995 Feb;2(2):89
Comment in: Acad Emerg Med. 1995 Feb;2(2):81-2

OBJECTIVE: To compare early and delayed blood administrations in animals subjected to near-fatal hemorrhage in the presence of a vascular injury and resuscitated to different mean arterial pressures (MAPs).

METHODS: Fifty-four immature swine with 4-mm infrarenal aortic tears were bled to a pulse pressure of 5 torr and then resuscitated (estimated blood loss 40 to 45 mL/kg). Groups I, II, and III were resuscitated with shed blood at a rate of 2 mL/kg/min, followed by normal saline at a rate of 6 mL/kg/min. Groups IV, V, and VI received the same fluids in reverse order. The fluids were infused intermittently to maintain MAPs of 40, 60, and 80 torr. The animals were observed for 60 minutes or until death.

RESULTS: The animals resuscitated to a MAP of 80 torr experienced significantly higher intraperitoneal hemorrhage volumes and mortality than did the animals intentionally maintained hypotensive, regardless of whether blood or normal saline was administered first. There was no significant difference in mortality or hemorrhage volumes between any of the groups intentionally maintained hypotensive. The animals maintained at a MAP of 60 torr were significantly less acidotic than were the animals resuscitated with the same fluid regimen but to a MAP of 40 torr. Early blood administration also minimized the acidosis associated with hypotensive resuscitation.

CONCLUSION: In this model of near-fatal hemorrhage with a vascular injury, maintenance of the hypotensive state produced comparable improvements in one-hour survival and reductions in hemorrhage volume regardless of whether blood or saline was administered first. Although hypotensive resuscitation resulted in improved outcome, it was associated with significant acidosis. This effect was minimized with moderate rather than severe underresuscitation and early blood administration.

Reviewer’s note:
54 swine bled to MAP 30 mmHg then Aortotomy performed
Resuscitated with shed blood plus Normal Saline to either MAP 40, 60 or 80mmHg.

  • Mortality: 78% if target was MAP 80mmHg
  • 22% if target was MAP 60mmHg
  • 11% if target was MAP 40mmHg (Lowest mortality with hypotensive resuscitation)

Improved outcome with fluid restriction in treatment of uncontrolled hemorrhagic shock.

Capone AC, Safar P, Stezoski W, Tisherman S, Peitzman AB.
Department of Surgery, University of Pittsburgh Medical Center, PA.

Journal of the American College of Surgeons. 1995 Jan;180(1):49-56

BACKGROUND: Recent studies have challenged current guidelines for prehospital fluid resuscitation. However, long-term studies evaluating the consequences of fluid restriction in uncontrolled hemorrhagic shock are lacking. This study was done to examine the long-term effects of deliberate hypotension in the treatment of uncontrolled hemorrhage.

STUDY DESIGN: Uncontrolled hemorrhagic shock was produced in 40 rats by a preliminary bleed (3 mL per 100 g) followed by 75 percent tail amputation. Experimental design consisted of three phases: a "prehospital phase" (90 minutes of uncontrolled bleeding with or without treatment with lactated Ringer's [LR] solution), followed by a "hospital phase" (60 minutes, including control of hemorrhage and fluid resuscitation including blood), and a three-day observation phase. Forty rats were studied in four treatment groups (ten rats per group). Group 1 consisted of untreated controls (no resuscitation). Group 2 had no fluid during the prehospital phase. Group 3 had prehospital resuscitation to a mean arterial pressure (MAP) of 40 mm Hg with LR, and group 4 had prehospital resuscitation to MAP of 80 mm Hg with LR. Groups 2, 3, and 4 received fluid and blood to MAP of 80 mm Hg and hematocrit of 30 percent in the hospital phase.

RESULTS: All rats in group 1 (untreated) died within 2.5 hours. Five rats in group 2 (no prehospital FR) survived 90 minutes; however, only one survived three days. In group 3, all ten rats survived 2.5 hours and six survived three days. In group 4, eight rats died within 90 minutes, but none survived long-term. Blood loss (mL per 100 g) for each group was 3.75 0.6 for group 1, 3.35 0.1 for group 2, 4.15 0.8 for group 3, and 8.45 0.6 for group 4, (p < 0.05, group 4 compared with groups 1, 2, and 3).

CONCLUSIONS: Attempts to achieve normal MAP during uncontrolled bleeding increased blood loss, hemodilution and mortality. Hypotensive resuscitation resulted in less acidemia and improved long-term survival. Reviewer’s Note: Improved outcome with fluid restriction in treatment of uncontrolled hemorrhagic shock - mortality at 90 min was least in the hypotensive resuscitation group.


Immediate versus delayed fluid resuscitation for Hypotensive patients with penetrating torso injuries

Bickell WH, Wall MH, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL,
Department of Emergency Services, Saint Francis Hospital,
Tulsa, Oklahoma, USA

N Engl J Med 1994 Oct 27; 331:1105-9
N Engl J Med 1994 Oct 27;331(17):1153-4
N Engl J Med 1995 Mar 9;332(10):681-3

BACKGROUND. Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma. The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso.

METHODS. We conducted a prospective trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg. The study setting was a city with a single centralized system of pre-hospital emergency care and a single receiving facility for patients with major trauma. Patients assigned to the immediate-resuscitation group received standard fluid resuscitation before they reached the hospital and in the trauma center, and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room.

RESULTS. Among the 289 patients who received delayed fluid resuscitation, 203 (70 percent) survived and were discharged from the hospital, as compared with 193 of the 309 patients (62 percent) who received immediate fluid resuscitation (P = 0.04). The mean estimated intraoperative blood loss was similar in the two groups. Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period, 55 (23 percent) had one or more complications (adult respiratory distress syndrome, sepsis syndrome, acute renal failure, coagulopathy, wound infection, and pneumonia), as compared with 69 of the 227 patients (30 percent) in the immediate-resuscitation group (P = 0.08). The duration of hospitalization was shorter in the delayed-resuscitation group.

CONCLUSIONS: For hypotensive patients with penetrating torso injuries, delay of aggressive fluid resuscitation until operative intervention improves the outcome.

Reviewer’s Note:
Prospective, randomized pre-hospital trial had 598 patients with penetrating torso trauma and systolic BP < 90
Initial BP averaged 72 mmHg in ‘limited’ resusc, 78mm in ‘standard’
Study comparing Standard resuscitation vs Limited resuscitation (until surgical intervention)
Limited resuscitation gave ~ 375 ml IV fluids - 30% mortality and 23% complication rate
Standard Resuscitation averaged 2,480 mls IV fluid - 38% mortality (p=0.04) and 30% complication rate
Higher than ‘limited fluid’ group.


Pulmonary edema and rapid transfusion: the comparison between rapid intravenous and intraarterial infusion in the severely hemorrhagic anesthesized pigs.

P'eng FK, Ho WM, Chan LP, Lin NN, Chen WY, Cheng FC, Kuo JS.
Veterans General Hospital-Taipei, Taiwan, R.O.C.

Zhonghua Yi Xue Za Zhi [a.k.a. Chung Hua i Hsueh Tsa Chih] (Taipei) 1994 Aug;54(2):73-81.

BACKGROUND. Patients with shock often develop pulmonary edema (PE) after rapid and massive fluid supplement and intravenous infusion. Rapid intraarterial infusion (RIA) is often used for fluid supplement in cardiac surgery, but has not yet been applied to treatment of hemorrhagic shock. However, by perfusing the ischemic peripheral organs through RIA, the fluid should flow first through the venous system to the heart and lung in less volume at lower speed. Therefore, the probability of developing PE should be less than that in rapid intravenous infusion (RIV) to the heart and lung in the same condition regarding volume and speed. Accordingly, we compared RIV and RIA in the treatment of hemorrhagic shock (HS) to determine if RIA provides any beneficial effect in reducing the development of PE.

METHODS. Eleven male mini-pigs weighing 17.5-32 kg were randomly divided into two groups to have RIV and RIA. Under general anesthesia, HS was induced by shedding blood (about 35 ml/kg) through the femoral artery until the mean arterial blood pressure (MAP) fell to 50 mm Hg. This condition was maintained for three hours. Then, lactated Ringer's solution (LRS) was infused thrice by force through a femoral artery (RIA) or an external jugular vein (RIV) at a speed of 25 ml/kg/min for 3 min. Data include hemodynamics, arterial blood gases, urine output, total extravascular lung water index (ETVI), and total amount of infused LRS used to induce gross PE (endotracheal release of pinkish foamy sputum). Serum concentrations of catecholamines, platelet activating factor (PAF) and thromboxane B2 (TxB2) were measured.

RESULTS. The total amount of LRS needed to induce gross PE was significantly greater in RIA than in RIV group. ETVI after rapid transfusion with a total of 225 ml/kg LRS was significantly less in RIA than in RIV group. Also, TxB2 concentrations in serum were less in RIA group. However, there was no difference in changes of hemodynamics, blood gases, acid-base, pulmonary shunting, urine output, serum concentrations of PAF or catecholamines between these two groups.

CONCLUSIONS. RIA may be a better choice for fluid replacement in HS in terms of decreasing the development of PE and lessening the release of ETVI and TxB2 in severely hemorrhagic anesthetized pigs. Further human investigation is warranted.

Reviewer’s note:
Arterial infusion of resuscitation fluids is perhaps a better choice than IV for rapid infusion of fluids. Arterial infusion causes significantly less pulmonary edema. There is also extensive literature from Russia/Eastern Europe supporting the intra-arterial route for resuscitation.


Resuscitation in uncontrolled hemorrhage.

Craig RL, Poole GV.
Dept. of Surgery, University of Mississippi Medical Center,
Jackson 39216-4505.

American Surgeon. 1994 Jan;60(1):59-62.

Fluid resuscitation is considered to be an integral component of the management of hemorrhagic shock. Numerous experimental studies of hypovolemic shock have confirmed the value of volume infusions, but in these models the rate, volume, and duration of bleeding are carefully controlled. The results of such studies may not be applicable to clinical hemorrhage, in which bleeding continues unabated. Male Sprague-Dawley rats weighing 250 to 390 g were anesthetized, and a femoral artery and vein were cannulated for constant blood pressure monitoring and fluid infusion. Through a midline abdominal incision, the distal ileocolic artery and vein were transected and allowed to bleed freely into the peritoneal cavity. The abdomen was closed and the animals were randomized to one of five groups: no resuscitation; small volume lactated Ringer's solution; large volume lactated Ringer's; small volume hetastarch; or large volume hetastarch. After 3 hours or at spontaneous death, blood was withdrawn to measure hematocrit, platelet count, and fibrinogen. Blood in the peritoneal cavity was collected and measured. Animals that received either lactated Ringer's or hetastarch had more bleeding into the peritoneal cavity and a greater dilution of clotting factors than animals that received no resuscitation fluids (P < 0.05). In addition, survival was highest in unresuscitated animals, although only the small volume hetastarch group had a significantly lower survival when independently compared with no resuscitation (P < 0.05). These results suggest that in traumatic shock, fluid resuscitation should be minimized until mechanical control of bleeding can be achieved.


The effects of isotonic saline volume resuscitation in uncontrolled hemorrhage.

Sindlinger JF, Soucy DM, Greene SP, Barber AE, Illner H, Shires GT.
Department of Surgery, Texas Tech University Health Sciences Center,
Lubbock 79430

Surg Gynecol Obstet. 1993 Dec;177(6):545-50.

In the present study, the effects of early isotonic fluid resuscitation on uncontrolled hemorrhage in rats under pentobarbital anesthesia were assessed. Forty-five female Sprague-Dawley rats, weighing between 230 and 295 grams, were anesthetized and cannulated. Uncontrolled hemorrhage was initiated by a 75 percent tail resection, and the rats were randomly divided into three groups: group 1, no resuscitation; groups 2 and 3, saline solution administration over a four minute interval (40 and 80 milliliters per kilogram, respectively), 15 minutes after the initial hemorrhage. Changes in blood pressure, blood loss and mortality rates were recorded and the rats were observed for up to 360 minutes. The mortality rates were 73, 40 and 53 percent for groups 1, 2 and 3, respectively. The corresponding average survival times for these groups were 135, 195 and 178 minutes. The difference between groups 1 and 2 were above the 95 percent confidence level using the chi-square test (mortality) and the Student's t test. The average total blood loss in groups 2 and 3 was 31.7 and 41.4 milliliters per kilogram of body weight; when compared with group 1 (24.6 milliliters per kilogram), the difference between the two latter groups (1 and 3) was statistically significant with a p < 0.001. These results suggest that early infusion of isotonic fluid improves survival time and reduces short term mortality in uncontrolled hemorrhage regardless of the associated increases in blood loss.

Reviewer’s note:
This is evidence that permissive hypotension may have limits/restrictions. In this experiment, fluid resuscitation increased survival time (but not overall mortality). Fluid resuscitation increased blood loss.


A computer model for analysis of fluid resuscitation.

Barnea O, Sheffer N.
Biomedical Engineering Program, Fleishmann Faculty of Engineering,
Tel Aviv University, Israel.

Comput Biol Med. 1993 Nov;23(6):443-54.

Injuries involving massive blood loss, such as burns, combat wounds, and injuries resulting from car accidents, require fluid resuscitation. The risk involved in fluid therapy is overloading of the circulation, resulting in pulmonary edema, which can lead to death. The risk of pulmonary edema may be eliminated by proper determination of maximal infusion volume and rate. Reabsorption of fluid from the extravascular compartment and infusion of fluid following blood loss results in reduction of the hematocrit. This is accompanied by an increase in the heart's preload and afterload. Coronary driving pressure and flow increase due to increased volume. However, because of the reduced hematocrit this increase in coronary flow may not be sufficient to compensate the myocardium, in terms of oxygen supply, for the increase in oxygen consumption. A model of the cardiovascular system, including an extravascular compartment, was designed to analyze the effects of fluid infusion on hemodynamic variables, cardiac oxygen balance, and the redistribution of fluid between intravascular and extravascular compartments. The results indicate that edema is not the only possible adverse effect of overloading the cardiovascular system with fluid. The simulation demonstrated that in certain cases the heart's oxygen balance can become negative. Limiting the rate of infusion can reduce this risk.


A comparison of the response of near-fatal acute hemorrhage models with and without a vascular injury to rapid volume expansion

Dronen SC, Stern SA, Wang X, Stanley M.
Department of Emergency Medicine, University of Cincinnati,
Ohio USA

Am J Emerg Med, 1993 July;11(4):331-5

Recent studies in which animals were bled from a vascular injury rather than an intravascular catheter demonstrate increased blood loss and mortality with rapid volume expansion. The purpose of this study was to better define the importance of incorporating a vascular injury in animal models of acute hemorrhage. We directly compared the response to resuscitation from hemorrhage of comparable severity in animals with and without a vascular injury. Thirty-four immature swine (14.6 to 23.2 kg) were instrumented and subjected to severe blood loss (40 to 46 mL/kg). Groups I and II were hemorrhaged from a femoral artery catheter only. Groups III and IV were initially bled in the same manner; however, when the mean arterial pressure (MAP) decreased to 30 mm Hg, a 4-mm tear was created in the infrarenal aorta, allowing free intraperitoneal hemorrhage. In all groups, the catheter hemorrhage was discontinued once the pulse pressure reached 5 mm Hg. Groups II and IV were resuscitated with normal saline (NS) infused at a rate of 6 mL/kg/min followed by shed blood at a rate of 2 mL/kg/min. The resuscitation fluids were infused as needed to maintain a MAP of 80 mm Hg. Groups I and III served as controls and were not resuscitated. All animals were observed for 60 minutes or until death. The data were compared using repeated measures analysis of variance with a post hoc Tukey Kramer and the Fisher's exact test. Mortality was 100%, 0%, 88%, and 78% for groups I, II, III, and IV, respectively (P < .05 for group II vs groups I, III, and IV).

Reviewer’s note:
The groups without fluid infusion had higher mortality in the first hour. The findings likely do not have clinical importance, since the experimenters did not follow the pigs beyond one hour – mortality may have been 100% in all groups if the experiment had been continued.


Effect of blood pressure on hemorrhage volume and survival in a near-fatal hemorrhage model incorporating a vascular injury.

Stern, SA Dronen SL, Birrer P. et al.
Department of Emergency Medicine, University of Cincinnati College of Medicine, Ohio.

Ann Emerg Med 1993 Feb;22 :155.
Comment in: Ann Emerg Med. 1993 Feb;22(2):225-6

STUDY HYPOTHESIS: In a model of near-fatal hemorrhage that incorporates a vascular injury, stepwise increases in blood pressure associated with aggressive crystalloid resuscitation will result in increased hemorrhage volume and mortality.

DESIGN: This study used a swine model of potentially lethal hemorrhage in the presence of a vascular lesion to compare the effects of resuscitation with mean arterial pressures of 40, 60, and 80 mm Hg. Twenty-seven fully instrumented immature swine (14.8 to 20 kg), each with a surgical-steel aortotomy wire in place, were bled continuously from a femoral artery catheter to a mean arterial pressure of 30 mm Hg. At that point the aortotomy wire was pulled, producing a 4-mm aortic tear and uncontrolled intraperitoneal hemorrhage. When the animal's pulse pressure reached 5 mm Hg, the femoral artery hemorrhage was discontinued and resuscitation was begun.

INTERVENTIONS: Saline infusion was begun at 6 mL/kg/min and continued as needed to maintain the following desired endpoints: group 1 (nine) to a mean arterial pressure of 40 mm Hg, group 2 (nine) to a mean arterial pressure of 60 mm Hg, and group 3 (nine) to a mean arterial pressure of 80 mm Hg. After 30 minutes or a total saline infusion of 90 mL/kg, the resuscitation fluid was changed to shed blood infused at 2 mL/kg/min as needed to maintain the desired mean arterial pressure or to a maximum volume of 24 mL/kg. Animals were observed for 60 minutes or until death.

MEASUREMENTS AND MAIN RESULTS: Data were compared using repeated-measures analysis of variance with a post hoc Tukey-Kramer, Fisher's exact test, and Kruskal-Wallis. Mortality was significantly greater in group 3 (78%) compared with either group 1 (11%; P = .008) or group 2 (22%; P = .028). Mean survival times were significantly shorter in group 3 (44 +/- 12 minutes) compared with either group 1 (58 +/- 6 minutes; P = .007) or group 2 (59 +/- 3 minutes; P = .006). The average intraperitoneal hemorrhage volumes were 13 +/- 14 mL/kg, 20 +/- 25 mL/kg, and 46 +/- 11 mL/kg for groups 1, 2, and 3, respectively (group 1 versus 2, P = .425; group 1 versus 3, P < .001; group 2 versus 3, P = .014). Group 2 animals demonstrated significantly greater oxygen deliveries compared with groups 1 and 3.

CONCLUSION: In a model of near-fatal hemorrhage with a vascular injury, attempts to restore blood pressure with crystalloid result in increased hemorrhage volume and markedly higher mortality.


Prospective evaluation of preoperative fluid resuscitation in hypotensive patients with penetrating truncal injury: a preliminary report.

Martin RR. Bickell WH. Pepe PE. Burch JM. Mattox KL.
Cora & Webb Mading Department of Surgery, Baylor College of Medicine,
Houston, Texas 77030.

Journal of Trauma. 1992 Sep;33(3):354-61; discussion 361-2,

Although intravenous (IV) fluid therapy is routinely prescribed for hypotensive injury victims, there are concerns that elevating the blood pressure before hemorrhage is controlled may be detrimental. This is a preliminary report of an ongoing randomized study designed to evaluate the effect fluid resuscitation, delayed until surgical intervention, has on the outcome for hypotensive victims of penetrating truncal injury. In the first year, 300 consecutive patients with gunshot or stab wounds to the trunk who had a systolic blood pressure of 90 mm Hg or less were entered into the study. Patients were excluded from the outcome analysis because of death at the scene or minor injury not requiring surgical intervention. The remaining study patients were randomized into (1) an immediate resuscitation group (n = 96) for whom IV fluid resuscitation was initiated in the ambulance and in the emergency center before surgical intervention, or (2) a delayed resuscitation group (n = 81) for whom IV fluid resuscitation was delayed until the time of surgical intervention. The two study groups were found to be well balanced with respect to anatomic injury severity, pretreatment vital signs, survival probability, and preoperative treatment times. There were no significant differences in the rate of survival to hospital discharge (immediate resuscitation group, 56%; delayed resuscitation group, 69%). There were no significant differences in the rate of postoperative complications. Further study is necessary to determine if it is advantageous to delay fluid resuscitation until surgical intervention.


Improved Outcome With Hypotensive Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

Kowalenko T, Stern S, Dronen S, Wang X
Department of Emergency Medicine, University of Cincinnati College of Medicine, Ohio.

Journal of Trauma 1992 Sep;33(3):349,1992:349-53; discussion 361-2

Recent animal studies have shown that aggressive saline infusion may produce significant mortality in models of moderately severe (20-30 mL/kg) uncontrolled hemorrhage. The postulated mechanism is an increase in hemorrhage that accompanies restoration of normal blood pressure. Although aggressive saline infusion and restoration of blood pressure appear indicated when hemorrhage is potentially lethal (40-45 mL/kg), we hypothesized that the attempt to restore blood pressure with aggressive saline infusion would not improve survival. This study used a swine model of severe uncontrolled hemorrhagic shock to compare the effects of resuscitation to mean pressures of 40 and 80 mm Hg. Twenty-four immature swine, each with a surgical steel aortotomy wire in place, were bled rapidly from a femoral artery catheter to a mean arterial pressure (MAP) of 30 mm Hg. The aortotomy wire was then pulled, producing a 4-mm aortic tear and free intraperitoneal hemorrhage. When the pulse pressure decreased to 5 mm Hg, saline infusion was begun at 6 mL/kg/minute and continued as needed to maintain the following endpoints: group I (MAP = 40 mm Hg), group II (MAP = 80 mm Hg), and group III (no resuscitation). After a maximum saline infusion of 90 mL/kg, the infusate was changed to shed blood at 2 mL/kg/minute. Data were compared using analysis of variance and Fisher's exact test. One-hour survival was 87.5%, 37.5%, and 12.5% for groups I, II, and III, respectively. Intraperitoneal hemorrhage for the three groups was 8.2 mL/kg, 39.9 mL/kg, and 6.7 mL/kg. The amount of saline infused was 55.8 mL/kg in group I and 90 mL/kg in group II.

Reviewer’s note:
60 minute survival rate was higher in the hypotensive resuscitation group (target BP = 40 mm Hg) than in the standard resuscitation group(target BP = 80mm Hg). Since the experiment ended after just 60 minutes, the clinical relevance is uncertain.


Use of Hypertonic Saline/Dextran Versus Lactated Ringer's Solution As a Resuscitation Fluid After Uncontrolled Aortic Hemorrhage in Anaesthetised Swine

Bickell WH, Bruttig SP, Millnamow GA, O’Benar J, Wade CE
Division of Military Trauma Research, Letterman Army Institute of Research,
Presidio of San Francisco, California.

Ann Emerg Med 1992 Sep;21(9):1077-1085

STUDY OBJECTIVE: We tested the hypothesis that following aortotomy, administration of hypertonic saline/dextran increases hemorrhage and mortality. We also compared hypertonic saline/dextran with the standard therapy of attempting to replace three times the amount of lost blood with lactated Ringer's solution.

DESIGN: In this model of uncontrolled arterial hemorrhage resulting from aortotomy, 24 anesthetized Yorkshire swine underwent splenectomy, stainless steel wire placement in the infrarenal aorta, and instrumentation with Swan-Ganz and carotid artery catheters. The wire was pulled, producing a 5-mm aortotomy and spontaneous intraperitoneal hemorrhage.

INTERVENTIONS: The animals were randomly assigned to one of three study groups: control; hypertonic saline/dextran group in which six minutes after aortotomy a 4-mL/kg mixture of IV 7.5% NaCl and 6% Dextran-70 was given over one minute; or lactated Ringer's group in which six minutes after aortotomy 80 mL/kg IV lactated Ringer's was given over nine minutes.

MEASUREMENTS AND MAIN RESULTS: The volume of hemorrhage and the mortality rate in hypertonic saline/dextran-treated animals were significantly greater than in the nonresuscitated controls (1,340 +/- 230 mL versus 783 +/- 85 mL and five of eight versus zero of eight, respectively; P less than .05). Although the mortality rate in the lactated Ringer's group was not significantly different from the hypertonic saline/dextran group, survival time was significantly shorter than in the hypertonic saline/dextran group.

CONCLUSION: In this model of uncontrolled hemorrhage, immediate IV administration of hypertonic saline/dextran significantly increased hemorrhage volume and mortality. However, the accentuation of hemorrhage and reduction in survival were not as great as that produced by the standard practice of attempting to replace the lost blood with three times that volume of lactated Ringer's.

Reviewer’s note:
They sought to compare hypertonic saline/dextran with lactated Ringer’s. The experiment uncovered the serendipitous result that 120 min survival was highest in control group (no fluid resuscitation) !


Saline resuscitation after fixed-volume hemorrhage. Role of resuscitation volume and rate of infusion.

Lilly MP, Gala GJ, Carlson DE, Sutherland BE, Gann DS.
Department of Surgery, University of Maryland, School of Medicine, Baltimore.

Annals of Surgery. 1992 Aug;216(2):161-71.

The authors have reported previously that small-volume resuscitation (1.8 x bled volume) with 0.9% NaCl restores blood volume and attenuates hormonal responses after large hemorrhage without correction of arterial hypotension. The authors studied the role of rate of infusion in this observation in chronically prepared dogs (aortic flow probe, right atrial pressure and volume, and arterial catheters) after 30% hemorrhage (24.1 0.4 mL/kg). After 30 minutes, subjects were observed either without treatment (no resuscitation) or with infusion of 43 mL/kg 0.9% NaCl over 3 hours by one of three protocols: (1) impulse infusion over 10 minutes, (2) variable rate infusion, bolus with tapering infusion, or (3) constant rate infusion. Significant improvement in cardiac output and in blood volume and significant decreases of vasopressin and arterial catecholamines were observed in all fluid-treated groups. This benefit was relatively independent of rate of infusion, although impulse infusion produced greater early improvement, which dissipated with time, and constant rate infusion produced better late results. In none of the fluid-treated groups were these improvements reflected in improved mean arterial pressure compared with the no resuscitation group.

The authors conclude that small-volume, slow-rate saline infusion produces physiologic benefits that cannot be assessed by easily measured clinical parameters. Thus, early resuscitation after trauma could aid patients even if arterial pressure is unchanged. This benefit might be even greater in patients with uncontrolled bleeding because arterial pressure, and hence bleeding, may not be increased by resuscitation of this type. A reassessment of the value of prehospital fluid resuscitation in the injured patient is warranted.


"Scoop and run" or stabilize hemorrhagic shock with normal saline or small-volume hypertonic saline?

Krausz MM, Bar-Ziv M, Rabinovici R, Gross D.
Department of Surgery, Hadassah University Hospital, Jerusalem, Israel.

J Trauma. 1992 Jul;33(1):6-10.

The controversy over a policy of "scoop and run" or stabilizing hemorrhagic shock when evacuation time is short has not yet been settled. Small volumes of hypertonic saline have been suggested as effective therapy when the scoop-and-run policy is adopted. In the present study small-volume hypertonic saline treatment and normal saline treatment of "uncontrolled" hemorrhagic shock (UCHS) in rats were compared with no treatment, which best simulates the scoop-and-run policy. The rats were randomly assigned to three groups. Uncontrolled hemorrhagic shock was induced by 12% resection of the terminal portion of the rats' tails. In group I (n = 13) the animals were untreated. In group II (n = 6) UCHS was treated by administering 41.5 mL/kg 0.9% NaCl (NS). In group III (n = 6) UCHS was treated by administering 5 mL/kg 7.5% NaCl (HTS). Resection of the rats' tails in group I was followed by bleeding of 3.3+/- 0.3 mL in 15 minutes with a fall in mean arterial pressure (MAP) from 100.9 7 to 63.5 5 mm Hg (p less than 0.001). The early bleeding and hemodynamic responses were similar in all three groups. Further blood loss in the first hour in group I was 0.5+/- 0.2 mL, and MAP rose spontaneously to 73.2+/- 6 mm Hg (p less than 0.05). The NS infusion in group II was followed by further bleeding of 4.1+/- 0.9 mL (p less than 0.01) and a further fall in MAP to 53.8+/- 7 mm Hg (p less than 0.01) after 60 minutes.

Reviewer’s note:
The rats whose bleeding was untreated had spontaneous improvement in blood pressure, and lower blood loss.
Fluid infusion led to greater bleeding.
See related work by the same research group, published in SGO, May 1992 and Archives of Surgery, January 1992 (below).


The combined effect of small volume hypertonic saline and normal saline solutions in uncontrolled hemorrhagic shock.

Krausz MM, Horn Y, Gross D.
Department of Surgery B, Hadassah University Hospital, Jerusalem.

Surg Gynecol Obstet. 1992 May;174(5):363-8.

Recently, small volume hypertonic saline solution (HTS) has been suggested for treatment of trauma casualties. Previously, we reported that small volume HTS treatment of uncontrolled hemorrhagic shock (UCHS) leads to increased bleeding, hemodynamic deterioration and early mortality. In the present study, large volume normal saline solution (NS) combined with small volume HTS was used to treat UCHS in rats. The rats were randomly assorted into four groups. Group 1 (n = 9) included rats in which UCHS induced by 12 per cent resection of the tail was untreated; group 2 (n = 8) consisted of those in which UCHS was treated after 15 minutes with 41.5 milliliters per kilogram of sodium chloride, 0.9 per cent (NS); group 3 (n = 7) included rats in which UCHS was treated with 5 milliliters per kilogram sodium chloride, 7.5 per cent (HTS); and group 4 (n = 9) included rats in which UCHS was treated by a combination of HTS and NS. In group 1, resection of the tail was followed by bleeding of 4.9 +/- 0.3 milliliters in 15 minutes, a decrease in mean arterial pressure (MAP) from 105 +/- 5 to 51 +/-3 torr (p less than 0.001) and pulse rate from 377 +/- 9 to 305 +/- 22 beats per minute (p less than 0.05). Further loss of blood after 30 minutes was 0.5 +/- 0.2 milliliters, MAP rose to 58 +/- 6 torr (p less than 0.05) with the death of two rats. Infusion of NS in group 2 was followed by further bleeding of 3.3 +/- 1.0 milliliters (p less than 0.01) and rise in MAP to 76+/- 9 after 30 minutes. Infusion of HTS in group 3 was followed by bleeding of 1.9+/- 0.3 milliliters (p less than 0.05) and fall in MAP to 57 +/- 14 torr (p less than 0.05). Continued loss of blood in this group resulted in further fall in MAP to 36 +/-11 torr (p less than 0.01) with death of 71 per cent (p less than 0.01) of the rats in four hours. Combined HTS and NS infusion in group 4 was followed by bleeding of 2.0 +/- 0.4 milliliters (p less than 0.05) and an increase in MAP to 93.0 +/- 3.0 torr (p less than 0.005) after 30 minutes with the death of only one animal in four hours. Total loss of blood in the three treated groups was similar and significantly higher than in the untreated group.


Hypertonic saline treatment of uncontrolled hemorrhagic shock at different periods from bleeding.

Krausz MM, Landau EH, Klin B, Gross D.
Department of Surgery B, Hadassah University Hospital, Jerusalem, Israel.

Archives of Surgery. 1992 Jan;127(1):93-6.

Hypertonic saline has been recently recommended for treatment of patients in hemorrhagic shock. Infusion of hypertonic saline at different periods in cases of uncontrolled hemorrhagic shock was studied in rats. The animals were divided into six groups: in group 1 uncontrolled hemorrhagic shock was induced by tail resection and no hypertonic saline was administered; in group 2 hypertonic saline was administered 5 minutes after shock was induced; in group 3 hypertonic saline was administered 15 minutes after shock was induced; in group 4 hypertonic saline was administered 30 minutes after shock was induced; in group 5 hypertonic saline was administered 60 minutes after shock was induced; and in group 6 hypertonic saline was administered 120 minutes after shock was induced. Tail resection in rats in group 1 was followed by a mean SEM bleeding of 2.7+/-.03 mL in 5 minutes. Infusion of hypertonic saline after 5 and 15 minutes resulted in additional bleeding of 6.3+/-1.0 mL and 3.8+/-0.5 mL, respectively, and a drop in mean arterial pressure to 36+/-8 mm Hg and 56+/-9 mm Hg, respectively. Mortality was 80% in group 2 and 53% in group 3. Infusion of hypertonic saline 30 and 60 minutes after shock was induced did not alter bleeding, mean arterial pressure, or survival. Infusion of hypertonic saline within 15 minutes of hemorrhagic shock resulted in increased bleeding, hypotension, and early death. Infusion 30 minutes or later did not alter these variables. This potential danger of early hypertonic saline therapy should be considered in the treatment of patients in trauma.


Future trends in emergency fluid resuscitation: Small-volume resuscitation by means of hypertonic saline Dextran

Kreimeier U, Messmer K.

Intensive Care World 1992; 9 (1): 16-20


The detrimental effects of intravenous crystalloid after aortotomy in swine.

Bickell, WH, Brutting SP, Millnamow GA, O’Benar J, Wade CE
Division of Military Trauma Research, Letterman Army Institute of Research,
Presidio of San Francisco, CA 94129-6800

Surgery 1991 Sep;110:529-536 Comment in: Surgery. 1991 Sep;110(3):573-4

We tested the hypothesis that, after aortotomy, rapidly replacing three times the blood volume deficit with intravenous crystalloid will increase hemorrhage and decrease survival. Sixteen anesthetized Yorkshire swine underwent splenectomy and stainless steel wire placement in the infrarenal aorta and were instrumented with pulmonary artery and carotid artery catheters. The wire was pulled, producing a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. The animals had been alternately assigned to either an untreated control group (n = 8) or a treatment group (n = 8), which received 80 ml/kg lactated Ringer's solution intravenously. The volume of hemorrhage and the mortality rate were significantly increased (p less than 0.05) in the treatment group receiving lactated Ringer's solution relative to the control animals (2142 178 ml versus 783 85 ml, and eight of eight animals versus zero of eight animals, respectively). From these data we conclude that, in this model of uncontrolled arterial hemorrhage resulting from abdominal aortotomy, rapidly administering lactated Ringer's solution intravenously significantly increases hemorrhage and death.


Control of bleeding is essential for a successful treatment of hemorrhagic shock with 7.5 per cent sodium chloride solution.

Rabinovici R, Krausz MM, Feuerstein G.
Department of Surgery, Jefferson Medical College, Philadelphia, Pennsylvania 19107.

Surg Gynecol Obstet. 1991 Aug;173(2):98-106.

Small volume hypertonic saline (HTS) solution resuscitation has been shown to restore hemodynamic derangements and to protect against mortality in "controlled" hemorrhagic shock (CHS), but it exacerbates the shock state in "uncontrolled" hemorrhagic shock (UCHS). To study the mechanisms associated with the divergent outcome of HTS treatment in CHS versus UCHS, HTS was administered to anesthetized rats (n = 7) subjected to 15 per cent resection of the tail followed by controlled or uncontrolled bleeding. HTS treatment of UCHS increased bleeding (13.3 +/- 1.6 milliliters, p less than 0.05), dropped mean arterial pressure (MAP) (-84.5 +/- 8.9 millimeters of mercury, p less than 0.001), central venous pressure (zero millimeters of mercury, p less than 0.001) and cardiac index (CI) (41 per cent of basal value, p less than 0.001) and increased acidosis (pH 7.23 +/- 0.12, p less than 0.05) and mortality (mean survival time 75 +/- 15 minutes versus 122 +/- 23 minutes of untreated rats, p less than 0.05). In contrast, when administered after application of a ligature proximal to the resection site (at 15 minutes), HTS completely reversed the changes in MAP, CI and total peripheral resistance index (TPRI), and improved mean survival time (172 +/- 7 minutes, p less than 0.05). These data support the assumption that HTS should be used in the treatment of hemorrhagic shock only after bleeding was controlled.


The effects of prehospital fluids on survival in trauma patients.

Kaweski SM, Sise MJ, Virgilio RW.
Trauma Research and Education Foundation, San Diego, California

J Trauma 1990;30(10):1215-1218 Comment in: J Trauma 1991 Sep;31(9):1325

The effect of prehospital intravenous fluids upon survival was studied in 6,855 trauma patients. Mean prehospital time was 36 minutes in both the group of patients who received fluids and the group that did not. The volume of fluid administered was not significantly different in the group who survived compared to those who died. Eighty-five per cent of the patients had an Injury Severity Score (ISS) less than 25 and the mortality rate in the 56% of patients in this group who received fluids was similar to that of the patients who did not receive fluids (0.7% vs. 0.5%). Twelve per cent of the patients had n ISS between 25 and 50. Sixty per cent of these patients received fluids and the mortality rates were similar to the patients who received fluids compared to those who did not (23% vs. 22%). Three per cent of patients had an ISS of greater than 50 and the mortality rate was highest in this group but was not influenced by the administration of fluids (90% vs. 86%). Comparison of groups with similar probability of survival according to the TRISS methodology also failed to show an influence of fluid administration on survival. The mortality rate in patients with an initial systolic blood pressure (BP) of 90 torr or greater was compared to the rate in patients with an admission BP less than 90 torr. Although hypotension was associated with a significantly higher mortality rate, the administration of fluids had no influence on this rate.


Early versus late fluid resuscitation: lack of effect in porcine hemorrhagic shock.

Chudnofsky CR, Dronen SC, Syverud SA, Hedges JR, Zink BJ.
Department of Emergency Medicine, University of Cincinnati, Ohio 45267-0769.

Ann Emerg Med. 1989 Feb;18(2):122-6.

The benefit of IV fluid therapy in the prehospital management of hemorrhagic shock is unproven. We used a reproducible, lightly anesthetized model of porcine continuous hemorrhage to evaluate the usefulness of pre-hospital IV fluid therapy. Incorporated into the model were time delays associated with ambulance request and dispatch, patient evaluation and treatment, and transport to the hospital in the average urban prehospital care system. Treatment occurred concurrently with hemorrhage. Twenty-eight immature swine (15 to 20 kg) were bled at a rate of 1.25 mL/kg/min. Animals in the prehospital IV group (n = 14) received fluid resuscitation at 1 mL/kg/min beginning 20 minutes after initiation of hemorrhage; those in the in-hospital IV group (n = 14) received fluid at a rate of 3 mL/kg/min beginning 35 minutes after hemorrhage. Both groups received blood and saline at 3 mL/kg/min 45 minutes after hemorrhage began, and both groups had hemorrhage controlled 25 minutes after simulated hospital arrival. Survival was 57% in both groups, and there were no statistically significant differences seen in measured hemodynamic or biochemical parameters. We conclude that early administration of IV normal saline has no effect on hemodynamics or survival in this porcine hemorrhagic shock model simulating an urban prehospital care system.


Fluid resuscitation after an otherwise fatal haemorrhage:

Traverso LW, Lee WP, Langford MJ.

I. Crystalloid solutions. Journal of Trauma 1986;26(2):168-75


Fluid resuscitation after an otherwise fatal haemorrhage: II. Colloid solutions.

Traverso LW, Hollenbach SJ, Bolin RB, Langford MJ, DeGuzman LR.

Journal of Trauma 1986;26(2):176-82

Reviewer's Note:
Although favouring aggressive fluid resuscitation, haemorrhage is controlled in these two studies prior to fluid administration and they are hence not applicable to the bleeding trauma patient population.


A Review of Postmortem Examinations in Combat Casualties

Strawitz JG , Scully R.E., Vickery A., Howard JM MC, USAR

Archives of Surgery 1955; 70: 260

Because of the clinical responsibilities of medical officers in a combat theater, complete postmortem examinations have seldom been routine. Pathologists are rarely available at a surgical hospital and frequently facilities for postmortem study are not available. Although it is obvious that combat casualties die from wounds received in action, the mechanisms of death are not clear. During a 10-month period in 1952 and 1953, autopsies were performed routinely by the Surgical Research Team in Korea at the 46th Surgical Hospital on the eastern front. Deaths were investigated which resulted from wounds received in combat, vehicular accidents, burns, medical illnesses, and self-inflicted injuries. This report deals only with 35 patients who died in the hospital after being wounded in combat. Analyses of the other traumatic deaths have been deleted in an effort to emphasize the problems encountered in treating the combat casualty…(See HTML link, above, for full text)


Surgery in World War II, General Surgery

Office of the Surgeon General.

US Government Printing Office; 1952


Experimental Haemorrhage Shock.

Wiggers CJ.

In: Physiology of Shock: The Commonwealth Fund, New York;1950. p. 121-143

Reviewer's Note:
Although favouring aggressive fluid resuscitation, haemorrhage is controlled in this model prior to fluid administration and hence not aplicable to the bleeding trauma patient population.


The Preventative Treatment of Wound Shock.

Cannon W, Fraser J, Cowell E.

JAMA 1918:618-621 7:10, October 2002