Resuscitation Regimens Research Articles

LACTATE PROFILES AS A RESUSCITATION ASSESSMENT TOOL IN A RAT MODEL OF BATTLEFIELD HEMORRHAGE RESUSCITATION

Time profiles of arterial lactate concentrations have been proposed as markers for both the degree of physiological derangement during shock and effectiveness of clinical resuscitation, but have not been evaluated for use in short-term experimental protocols. We developed two quantitative mixed models of sequential arterial lactate concentrations to evaluate competing low-volume (<4 mL/kg) battlefield resuscitation therapies in a rat model of acute severe hemorrhagic shock: a simple linear additive model and a nonlinear mechanistic model that described lactate profiles in a continuous trajectory with a defined turning point. Data were obtained during a study evaluating a novel hemoglobin polymer (OxyVita) in a cocktail of hypertonic saline and Hextend as an alternative to standard Hextend. Fluids were either infused by titration to a mean systolic pressure of 60 mmHg or as a single bolus. Parameter estimates derived from both models were assessed for evidence of treatment efficacy and as indicators of short-term survival. A cocktail of hypertonic saline and Hextend was superior to standard Hextend in enhancing survival; however, lactate profiles did not differ between treatments. Regardless of resuscitation regimen, animals surviving to at least 60 min posthemorrhage can be discriminated from nonsurvivors by significantly lower peak lactates (a difference of at least 3 mM; P < 0.001), and all survivors exhibited a decline in lactate with resuscitation. Sequential measurements of lactate over relatively short time frames during resuscitation are of value in assessing both response to resuscitation and short-term mortality.

Postresuscitation Tissue Neutrophil Infiltration is Time-Dependent and Organ-Specific

Hemorrhagic shock with conventional resuscitation (CR) primes circulating neutrophils and activates vascular endothelium for increased systemic inflammation, superoxide release, and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) with intraperitoneal instillation of a clinical peritoneal dialysis solution decreases systemic inflammation and edema formation by enhancing tissue perfusion. The aim of this study is to determine the effect of adjunctive DPR on neutrophil and fluid sequestration. Anesthetized rats were hemorrhaged to 40% mean arterial pressure for 60 min. Animals were randomized for CR with the return of the shed blood plus two volumes of saline, or CR plus adjunctive DPR with 30 mL of intraperitoneal injection of a clinical peritoneal dialysis solution. Tissue myeloperoxidase (MPO) level, a marker of neutrophil sequestration, and total water content were assessed in the gut, lung, and liver in sham animals and at time-points 1, 2, 4, and 24 h postresuscitation. Resuscitation from hemorrhagic shock increases MPO level in all tissues in a near-linear fashion during the first 4 h following resuscitation. This occurs irrespective of the resuscitation regimen used. Tissue MPO level returned to baseline at 24 h following resuscitation except in the liver where CR and not adjunctive DPR caused a significant rebound increase. Adjunctive DPR prevented the CR-mediated obligatory fluid sequestration in the gut and lung and maintained a relative normal tissue water in these organs compared with CR alone (n = 7, F = 10.1, P < 0.01). Hemorrhagic shock and resuscitation produces time-dependent organ-specific trends of neutrophil sequestration as measured with tissue levels of myeloperoxidase, a marker of neutrophil infiltration. Modulation of the splanchnic blood flow by direct peritoneal resuscitation did not alter the time-dependent neutrophil infiltration in end-organs, suggesting a subordinate role of blood rheology in the hemorrhage-induced neutrophil sequestration. Vulnerable window for neutrophil-mediated tissue damage exists during the first 4 h following resuscitation from hemorrhagic shock in rats. Direct peritoneal resuscitation prevents the early obligatory fluid sequestration and promotes early fluid mobilization.

Hypertonic saline resuscitation improves intestinal microcirculation in a rat model of hemorrhagic shock

Conventional resuscitation (CR) from hemorrhagic shock (HS) often restores and maintains hemodynamics but fails to restore intestinal perfusion. Post-CR intestinal ischemia has been implicated in the initiation of a gut-derived exaggerated systemic inflammatory response and in the progressive organ failure following HS. We propose that intestinal ischemia can be prevented with hypertonic saline resuscitation (HTSR). Anesthetized male Sprague-Dawley rats (200 to 215 g) were hemorrhaged to 50% of mean arterial pressure (MAP) for 60 minutes and randomly assigned to 1 of the resuscitation groups (n = 7 each): Group I: sham operation and no HS; Group II: HS + CR with the return of the shed blood + 2 volumes of normal saline (NS); Group III: HS + return of the shed blood + hypertonic saline (HTS); (7.5 % NaCl, 4 ml/kg); Group IV: HS + HTS, then return of the shed blood after 60 minutes; Group V: HS + HTS, then 1 volume of NS after 60 minutes. Microvascular diameters of inflow (A1) and proximal and distal premucosal arterioles (A3) in terminal ileum and flow in A1 were measured using in vivo videomicroscopy and optical Doppler velocimetry. Hematocrit, plasma osmolarity, and electrolytes were measured in Groups II and III. HS caused a selective vasoconstriction in A1 arterioles that was not seen in the premucosal arterioles. CR restored and maintained MAP and caused generalized, progressive vasoconstriction at all intestinal arteriolar levels that is associated with hypoperfusion. HTSR failed to restore or maintain MAP or intestinal A1 arteriolar blood flow until the shed blood was returned. However, HTSR prevented the post-resuscitation, premucosal vasoconstriction and produced an insidious selective vasodilation in the A3 arterioles, which was most significant with early blood return (Group III). This selective arteriolar vasoactivity was associated with a significant improvement of endothelial cell function. Plasma hyperosmolality and hypernatremia persisted during the entire 2 hours post-resuscitation with HTS. Small-volume HTSR can be used as a resuscitation regimen at the trauma scene and for selective clinical conditions where hypotensive resuscitation is indicated. HTSR improves intestinal perfusion by selective vasodilation of the precapillary arterioles even at MAP close to shock levels.

THE CELLULAR, METABOLIC, AND SYSTEMIC CONSEQUENCES OF AGGRESSIVE FLUID RESUSCITATION STRATEGIES

Increasing evidence has demonstrated that aggressive crystalloid-based resuscitation strategies are associated with cardiac and pulmonary complications, gastrointestinal dysmotility, coagulation disturbances, and immunological and inflammatory mediator dysfunction. As large volumes of fluids are administered, imbalances in intracellular and extracellular osmolarity occur. Disturbances in cell volume disrupt numerous regulatory mechanisms responsible for keeping the inflammatory cascade under control. Several authors have demonstrated the detrimental effects of large, crystalloid-based resuscitation strategies on pulmonary complications in specific surgical populations. Additionally, fluid-restrictive strategies have been associated with a decreased frequency of and shorter time to recovery from acute respiratory distress syndrome and trends toward shorter lengths of stay and lower mortality. Early resuscitation of hemorrhagic shock with predominately saline-based regimens has been associated with cardiac dysfunction and lower cardiac output, as well as higher mortality. Numerous investigators have evaluated potential risk factors for developing abdominal compartment syndrome and have universally noted the excessive use of crystalloids as the primary determinant. Resuscitation regimens that cause early increases in blood flow and pressure may result in greater hemorrhage and mortality than those regimens that yield comparable flow and pressure increases late in resuscitation. Future resuscitation research is likely to focus on improvements in fluid composition and adjuncts to administration of large volume of fluid.

Closed-Loop Resuscitation of Burn Shock

Fluid therapy for burn shock is adjusted to establish a target level of urinary output. However, the means for adjusting infusion rate are not defined. Our objective was to compare the performance of automated computer-controlled resuscitation with manual control for burn resuscitation. Sheep with a 40% TBSA full-thickness burn, administered under halothane anesthesia, were resuscitated to restore and maintain normal sheep urinary outputs in a target range of 1 to 2 ml/kg per hour over the course of 48 hours using closed-loop resuscitation (n = 10) or manual hourly adjustment of infusion rate (n = 11). The automated closed-loop resuscitation system is based on a proportional-integral-derivative algorithm, which adjusted infusion rate based on continuous monitoring and changes in urinary output. Mean urinary outputs over the course of 48 hours were in target range and were virtually identical at 1.9 +/- 0.5 ml/kg per hour for the closed-loop group and 2.0 +/- 0.7 ml/kg per hour for the technician group. Mean infusion rates and infused volumes also were similar. The closed-loop group exhibited significantly lower hourly variation for both urinary output and infusion rate compared hourly control. Hourly targets were achieved in 41% of the measurements in technician group compared with 48% for the closed-loop group (P = .23). Hourly urinary output in the technician group was undertarget by 25% as opposed to 16% with the closed-loop group (P = .02). Automated closed-loop control of infusion rates after burn injury produced urinary outputs in target ranges with less variation and less under target values than manual hourly adjustments. Closed-loop resuscitation may provide an improvement over current resuscitation regimens.

Validation of Stroke Work and Ventricular Arterial Coupling as Markers of Cardiovascular Performance during Resuscitation

Resuscitation regimens based on stroke work index (SWI) and ventricular-arterial coupling (VAC) are controversial. The Signal Interpretation and Monitoring (SIMON) system continuously collects and stores physiologic intensive care unit (ICU) bedside data at 3- to 5-second intervals. The purpose of this study was to demonstrate the capabilities of a completely automated data management system by further evaluating SWI-based resuscitation. This study was a retrospective review of all severely injured patients requiring a pulmonary artery catheter (PAC) for acute postinjury resuscitation. Patients with a severe head injury were excluded. Hemodynamic (HD) data (21 million datapoints) were densely acquired and archived by SIMON. Mean values of HD variables were compared between survivors and nonsurvivors. Receiver operator characteristic (ROC) curves were constructed for HD variables. Threshold values which maximized sensitivity and specificity were determined. Eighty-eight patients over a 19-month time period met criteria and were included in the analysis. SWI was significantly greater in survivors versus nonsurvivors (4421 +/- 1278 versus 3163 +/- 1066 mm Hg . mL/m, p = 0.0008). VAC was quantified by the ratio (RATIO) of afterload (Ea) to contractility (Ees). RATIO (Ea/Ees) in survivors was significantly better than in nonsurvivors (1.9 +/- 1.1 vs. 2.9 +/- 1.0, p = 0.002). ROC curves identified threshold values of 3250 mm Hg x mL/m for SWI and 2.1 for RATIO (AUC = 0.78 and 0.82, respectively). Previous work demonstrating the use of SWI and VAC as resuscitation guidelines was supported through the use of a powerful ICU data management system (SIMON). The emergence of these "new vital signs" may change the way injured patients are evaluated and resuscitated in the ICU.

Prehospital Management and Fluid Resuscitation in Hypotensive Trauma Patients Admitted to Karolinska University Hospital in Stockholm

Few previous studies have been conducted on the prehospital management of hypotensive trauma patients in Stockholm County. The aim of this study was to describe the prehospital management of hypotensive trauma patients admitted to the largest trauma center in Sweden, and to assess whether prehospital trauma life support (PHTLS) guidelines have been implemented regarding prehospital time intervals and fluid therapy. In addition, the effects of the age, type of injury, injury severity, prehospital time interval, blood pressure, and fluid therapy on outcome were investigated. This is a retrospective, descriptive study on consecutive, hypotensive trauma patients (systolic blood pressure < or = 90 mmHg on the scene of injury) admitted to Karolinska University Hospital in Stockholm, Sweden, during 2001-2003. The reported values are medians with interquartile ranges. Basic demographics, prehospital time intervals and interventions, injury severity scores (ISS), type and volumes of prehospital fluid resuscitation, and 30-day mortality were abstracted. The effects of the patient's age, gender, prehospital time interval, type of injury, injury severity, on-scene and emergency department blood pressure, and resuscitation fluid volumes on mortality were analyzed using the exact logistic regression model. In 102 (71 male) adult patients (age > or = 15 years) recruited, the median age was 35.5 years (range: 27-55 years) and 77 patients (75%) had suffered blunt injury. The predominant trauma mechanisms were falls between levels (24%) and motor vehicle crashes (22%) with an ISS of 28.5 (range: 16-50). The on-scene time interval was 19 minutes (range: 12-24 minutes). Fluid therapy was initiated at the scene of injury in the majority of patients (73%) regardless of the type of injury (77 blunt [75%] / 25 penetrating [25%]) or injury severity (ISS: 0-20; 21-40; 41-75). Age (odds ratio (OR) = 1.04), male gender (OR = 3.2), ISS 21-40 (OR = 13.6), and ISS >40 (OR = 43.6) were the significant factors affecting outcome in the exact logistic regression analysis. The time interval at the scene of injury exceeded PHTLS guidelines. The vast majority of the hypotensive trauma patients were fluid-resuscitated on-scene regardless of the type, mechanism, or severity of injury. A predefined fluid resuscitation regimen is not employed in hypotensive trauma victims with different types of injuries. The outcome was worsened by male gender, progressive age, and ISS > 20 in the exact multiple regression analysis.

Endothelial Dysfunction After Lactated Ringerʼs Solution Resuscitation for Hemorrhagic Shock

Endothelial dysfunction is presumed to occur after hemorrhagic shock and resuscitation. This study uses a novel large-animal model to evaluate the effects of diverse resuscitation regimens on endothelial function. Twenty-seven adult domestic pigs (Sus scrofa) were used in this study. Control pigs (n = 3) underwent instrumentation alone. The remaining pigs experienced controlled hemorrhagic shock to a mean arterial blood pressure of 30 +/- 5 mm Hg for 45 minutes. Pigs were resuscitated to their baseline mean arterial blood pressure +/-5 mm Hg with either shed blood (SB; n = 8), lactated Ringers solution (40 mL/kg) followed by shed blood (LRSB; n = 8), or lactated Ringers solution alone (LR; n = 8). At baseline, 1 and 4 hours after resuscitation, acetylcholine (5, 10, and 15 microg/min) was infused into the proximal iliac artery to measure endothelial dependent relaxation (EDR). Sodium nitroprusside was infused to determine endothelial independent relaxation at the end of the study to insure smooth muscle vasomotor integrity. External iliac artery luminal diameter was measured using motion-mode ultrasonography. Statistical analysis was performed using repeated-measures analysis of variance with Tukey's post-hoc analysis. All pigs survived the experiment. Pigs required ninefold more resuscitation with LR (370.58 +/- 29 mL/kg) versus SB (41.45 +/- 3.5 mL/kg) or LRSB (76.4 +/- 1.1 mL/kg) (p < 0.05). EDR for LR pigs 1 hour after initiation of resuscitation (R1) was 70.4 +/- 14.4% compared with 94.2 +/- 13.4% for SB and 106.1 +/- 8.2% for LRSB (p < 0.05). At 4 hours after resuscitation (R4), systolic luminal diameters were larger in the SB (0.45 +/- 0.01 cm) and LRSB (0.51 +/- 0.02 cm) groups compared with LR (0.41 +/- 0.03 cm) (LRSB versus LR; p = 0.01). At R4, EDR for the LR group was 78.3 +/- 10.7% compared with SB (101.4 +/- 8.3%) and LRSB (106.4 +/- 7.4%) (p < 0.05). Infusion of sodium nitroprusside confirmed integrity of smooth muscle vasorelaxation. Analysis of serum nitric oxide levels revealed decreased values after resuscitation with LR (9.44 +/- 0.76 mol/L) compared with SB (26.3 +/- 7.8 mol/L) and LRSB (16.3 +/- 1.0 mol/L) (p = not significant). This is the first description of a large-animal model to evaluate EDR after hemorrhagic shock. Resuscitation with LR requires significantly larger volumes than SB or LRSB. LR resuscitation leads to endothelial dysfunction, as determined by decreased EDR, versus SB or LRSB. Resuscitation with blood products may preserve nitric oxide bioactivity when compared with crystalloid resuscitation in the setting of hemorrhagic shock.

HIGH-DOSE VITAMIN C INFUSION REDUCES FLUID REQUIREMENTS IN THE RESUSCITATION OF BURN-INJURED SHEEP

Fluid resuscitation to maintain adequate tissue perfusion while reducing edema in the severely burned patient remains a challenge. Recent studies suggest that reactive oxygen species generated by thermal injury are involved in edema formation associated with burn. The present study tested the hypothesis that adding a free radical scavenger to the resuscitation fluid would reduce total fluid requirements in the treatment of severe thermal injury. Anesthetized chronically instrumented sheep received a 40% total body surface area full-thickness flame burn. At 1 h after injury, animals were resuscitated with lactated Ringer's (LR, n = 14) as control, LR containing high doses of vitamin C (VC, n = 6), 1000 mOsM hypertonic saline (HS, n = 7), or 1000 HS containing VC (HS/VC, n = 7) in coded bags so that investigators were blinded to the treatment. Fluids were infused at an initial Parkland rate of 10 mL/kg/h, adjusted hourly to restore and maintain urine output at 1 to 2 mL/kg/h. Sheep in the VC or HS/VC group received 250 mg/kg VC in the first 500 mL of LR or HS, and then 15 mg/kg/h thereafter. Hemodynamic variables and indices of antioxidant status were measured. At 48 h postburn, sheep were euthanized, and heart, liver, lung, skeletal muscle, and ileum were evaluated for antioxidant status. All fluid resuscitation regimens were equally effective in restoring cardiac output to near baseline levels; no treatment effects were apparent on arterial pressure or heart rate. VC infusion significantly reduced fluid requirements and, therefore, net fluid balance (fluid in, urine out) by about 30% at 6 h and about 50% at 48 h in comparison with the LR group (P < 0.05). HS and HS/VC reduced fluid requirements by 30% and 65%, respectively, at 6 h, but the volume-sparing effect of HS was not observed after 36 h and that of HS/VC was lost after 12 h. Plasma total antioxidant potential increased about 25-fold (P < 0.05) at 2 and 3 h in response to VC infusion compared with the LR and HS groups, and remained about 5- to 10-fold higher throughout the rest of the study. VC infusion also prevented the 4-fold increase in plasma thiobarbituric acid reactive substances seen in the LR group early after burn (P < 0.05). Tissue antioxidant status was similar between groups. In this sheep burn model, continuous high-dose VC infusion reduced net fluid balance, reduced indices of plasma lipid peroxidation, and maintained overall antioxidant status in comparison with standard-of-care LR treatment.

N-Acetylcysteine administered as part of the immediate post-traumatic resuscitation regimen does not significantly influence initiation of inflammatory responses or subsequent endotoxin hyporesponsiveness

Polytrauma and resuscitative efforts induce extensive alterations in the host's internal environment and cellular responses that may be a serious threat to these patients. Administration of exogenous thiols has been recommended to modulate the post-traumatic inflammatory responses. In this study, we have investigated the effect of N-acetylcysteine (NAC) on the early markers of leukocyte activation and subsequent endotoxin hyporesponsiveness. Twenty-eight pigs were exposed to a standardized gunshot injury. First aid treatment and initial life saving surgery was started without delay. One group ( n = 14) was randomised to receive NAC 200 mg kg −1 over 20 min, the remaining group was given the same volume of vehicle. Blood samples drawn at time points 0 and 75 min were also studied in vitro and stimulated with LPS or LPS plus NAC. Selected physiologic variables and degree of organ injury were equal in both groups. TNF-α, IL-1β, and reactive oxygen species (ROS) tended to be lower in the NAC-group (NS). In vitro, NAC significantly reduced the release of the same cytokines after the LPS challenge in blood drawn before injury. NAC did not influence post-traumatic endotoxin tolerance. Adding NAC to the immediate resuscitation fluid did not influence the early post-traumatic organ injury, and initiation of inflammatory responses significantly, or endotoxin tolerance. In vitro, NAC significantly reduced proinflammatory cytokine release, but only in normal blood. The clinical value of this treatment regimen is probably restricted, both due to the unfavourable post-traumatic internal environment and imposed dosing limitations.

The isomeric composition of lactated Ringer’s has no differential effect on gastric dysfunction after mesenteric ischemia/reperfusion

Lactated Ringer’s is the standard of care trauma resuscitation, but the D-isomer of lactate has been shown to activate proinflammation. We have shown that superior mesenteric artery occlusion (SMAO) without resuscitation causes gastric dysfunction characterized by luminal fluid accumulation and alkalization. In the same model, LR resuscitation protected the ileum, but the presence of the D-isomer abrogated this effect. We, therefore, hypothesized that the isomeric composition of LR resuscitation would have a differential effect on gastric dysfunction and inflammation in this model. Rats underwent sham or SMAO for 60 min. Five minutes prior to clamp removal, SMAO animals received no resuscitation, 20 ml/kg IV (our standard) of either LL or LD isomer LR, or 17 ml/kg IV normal saline (NS) as equal salt load control. Animals were sacrificed at 6 h of reperfusion and gastric mucosa was harvested for analysis. Gastric dysfunction was quantitated by gastric volume and luminal pH. Heme-Oxygenase-1 (HO-1; index of anti-inflammation) and inducible Nitric Oxide Synthase (iNOS; index of proinflammation) protein expression were analyzed by Western immunoblot. Data are reported as mean ± SEM ( n > 6/group; ANOVA). Means with different letters are significantly different. SMAO (no resuscitation) increased gastric volume and pH. All three resuscitative regimens decreased gastric volume, had no effect on pH, and equally induced HO-1 and iNOS. In conclusion, isomeric composition of LR had no differential effect on gastric dysfunction and inflammation after SMAO in contradistinction to its previously observed effects in the ileum. The isomeric immunomodulatory effects of LR appear to be organ specific. TABLE—ABSTRACT P87 Model Volume (ml) pH (pH) HO-1 (AU) iNOS (AU) Sham 0.30 ± 0.05 a 1.67 ± 0.16 a 0.36 ± 0.02 a 0.28 ± 0.03 a SMAO 2.22 ± 0.57 b 6.58 ± 0.20 b 0.43 ± 0.05 a 0.29 ± 0.07 a SMAO/LL 1.28 ± 0.31 c 5.58 ± 0.62 b 0.56 ± 0.04 b 0.50 ± 0.06 b SMAO/LD 0.80 ± 0.23 c 6.38 ± 0.38 b 0.57 ± 0.04 b 0.44 ± 0.03 b SMAO/NS 1.03 ± 0.12 c 5.83 ± 0.60 b 0.59 ± 0.05 b 0.49 ± 0.10 b

Attenuation of leukocyte adhesion by recombinant TNF-binding protein after hemorrhagic shock in the rat.

Ischemia/reperfusion injury involves a large number of humoral and cellular mediators that activate leukocytes that subsequently migrate to local tissues. Tumor necrosis factor (TNF)-alpha may be one of the most important mediators of this post-shock inflammatory response. In this study, we investigated the influence of a recombinant Type I (55 kDa) TNF-binding protein (TNF-BP) on leukocyte-endothelial interactions in the liver after hemorrhagic shock. Hemorrhagic shock was induced in female Sprague-Dawley rats (40 mmHg for 90 min) and a standardized resuscitation regimen was applied. At the time of resuscitation, animals were treated intravenously with either TNF-BP 4 mg/kg or placebo. The liver microcirculation was investigated using intravital fluorescence microscopy and immunohistochemistry at 5 h and 48 h after reperfusion. At 5 h, treatment with TNF-BP significantly reduced temporary leukocyte adhesion in the liver sinusoids as well as mean adhesion time of leukocytes in the hepatic central vein. In contrast, after 48 h, permanent leukocyte adhesion in the central hepatic vein was significantly reduced in the group receiving TNF-BP, whereas temporary leukocyte adhesion and mean adhesion time did not differ between the two groups. Both types of leukocyte adhesion, rolling adhesion after 5 h and firm adhesion after 48 h, were reduced in the group treated with TNF-BP, thereby suggesting a long-lasting anti-inflammatory effect.

Endocrine targets in experimental shock.

Modified resuscitation regimens and cytokine blockade/receptor antagonism after trauma have not been successful in decreasing the mortality rates from sepsis in trauma patients; therefore, an alternative approach using endocrine targets as modulators or inhibitors may be useful. Information regarding the influence of gender and hormones on immune and cardiovascular responses after nonthermal trauma-hemorrhagic shock is, on the one hand, considerable but, on the other hand, disappointingly incomplete. Trauma-hemorrhagic shock produces gender dimorphic immune and cardiovascular responses; men exhibit cardiovascular depression and are immunosuppressed, whereas proestrus women do not show cardiovascular or immunologic depression under those conditions. Furthermore, experimental studies have demonstrated the use of hormones, hormone antagonists, sex steroids, and receptor antagonists as salutary adjuncts, without any adverse effects on gastrointestinal, hepatic, and renal functions, for restoring the depressed immune and cardiovascular responses after trauma-hemorrhage. Thus, flutamide, dehydroepiandrosterone, metoclopramide, and 17beta-estradiol, which are readily availably clinically and do not produce any adverse hemodynamic effects, appear to be safe and novel agents/hormones for the treatment of immune and cardiovascular depression after severe blood loss in male and female trauma victims.

Resuscitation regimens for hemorrhagic shock must contain blood.

Endothelial cell dysfunction occurs during hemorrhagic shock (HS) and persists despite adequate resuscitation (RES) that restores and maintains hemodynamics. We hypothesize that RES from HS with crystalloid solutions alone aggravate the endothelial cell dysfunction. To test this hypothesis, anesthetized nonheparinized rats were monitored for hemodynamics, and the terminal ileum was studied with intravital video microscopy. HS was 50% of mean arterial pressure (MAP) for 60 min. Four hemorrhaged groups (10 animals in each group) were randomized for RES: group I with shed blood returned + equal volume of normal saline (NS); group II with shed blood returned + 2x NS; group III with 2x NS only; and group IV with 4x NS only. Two hours post-RES, endothelial cell function was assessed with the endothelial-dependent agonist acetylcholine (ACh, 10(-9)-10(-4) M). Maximum arteriolar diameter was elicited by the endothelial-independent agonist sodium nitroprusside (NTP, 10(-4) M). HS caused a selective vasoconstriction associated with low blood flow in inflow A1 arterioles in all hemorrhaged groups. Post-RES vasoconstriction developed in A1 and premucosal arterioles (pA3 and dA3) In all hemorrhaged groups regardless of the RES regimen. However, A1 vasoconstriction and flow were significantly worst in the animals RES with NS alone (-43% and -75%, respectively) compared with those resuscitated with blood and NS (-27% and -57%). Impaired dilation response to ACh was noted in all hemorrhaged animals. However, a significant shift to the right of the dose-response curve (decreased sensitivity) was observed in the animals resuscitated with NS alone irrespective of the RES volume. These animals required at least two orders of magnitude greater ACh concentration to produce a 20% dilation response. For all vessel types, Group II had the best preservation of endothelial cell function. In conclusion, HS causes a selective vasoconstriction of A1 arterioles, which was not observed in A3 vessels. RES from HS results in progressive vasoconstriction in all intestinal arterioles irrespective of the RES regimen. Crystalloid RES after HS does not restore hemodynamics to baseline and is associated with a marked endothelial cell dysfunction. Blood-containing RES regimens preserve and maintain hemodynamics and are associated with the least microvascular dysfunction. Therefore, regimens for RES from HS must contain blood. Endothelial cell dysfunction is not the sole etiologic factor of post-RES microvascular impairment.

Effects of three different resuscitation regimens on jejunal tissue oxygen supply after hemorrhagic shock

In this study we evaluated effects of blood (B; n = 7), gelatine (G; n = 8) and Ringer's lactate (R; n = 8) resuscitation on jejunal microvascular blood flow (PU), tissue microvascular hemoglobin oxygen saturation (HbO2t) and jejunal mucosal tissue oxygen tension (PO2muc) after severe haemorrhage (50% of estimated blood volume) in pigs.

Resuscitation regimens of hemorrhagic shock must contain blood.

Resuscitation regimens of hemorrhagic shock must contain blood.

Lung perfusion in hemorrhagic shock of rats: the effects of resuscitation with whole blood, saline or Hes 6%.

This study was undertaken to determine the effects of various resuscitation regimens on lung perfusion following resuscitation from hemorrhagic shock. Fourty male Sprague-Dawley rats (250-300 g) were used. The rats were divided randomly into four groups (n = 10 for each) and were sedated with intramuscular ketamine (100 mg/kg). We measured blood pressure, rectal temperature and lung perfusion using radioscintigraphy with a technetium colloid indicator. The systolic blood pressure was decreased 75% by removing blood via v. jugularis in the first three groups and group 4 was accepted as the control group, and blood volume was not diminished. Then the first three groups were resuscitated with autologous blood containing 125 units heparine/ml in group 1, saline in group 2, and hydroxyethyl starch (HES) 6% in group 3. After the correction of hypovolemia, all animals were injected 100 Bg (0.1 cc) technetium 99 m macroaggregated albumin (99mTc MAA) via penil vein. After injection of 99mTc MAA, 3 minutes fixed images were detected by a y camera in posterior position at 15 minutes and 5 hours. 99mTc MAA "wash out" rate in lung was determined quantitatively at 5 hours. Compared to a control group, lung perfusion was decreased significantly in groups resuscitated with saline, and HES 6% while perfusion was restored with autologous blood. We conclude that heparinized autologous blood saved lung capillary circulation in hemorrhagic shock in rats.

International Trauma Anesthesia and Critical Care Society (ITACCS).

International Trauma Anesthesia and Critical Care Society (ITACCS).

Resuscitation of severe uncontrolled hemorrhage: 7.5% sodium chloride/6% dextran 70 vs 0.9% sodium chloride.

Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20 mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.

Pentoxifylline fails to improve organ dysfunction and survival when used in the resuscitation of a porcine model of haemorrhage and abdominal sepsis

Pentoxifylline is a phosphodiesterase inhibitor, known to suppress tumour necrosis factor-alpha production and improve cardiopulmonary parameters and survival in animal models of sepsis. Using a porcine model of abdominal trauma resulting from the combined insults of haemorrhage and infection, a randomised placebo-controlled trial was conducted of pentoxifylline (20 mg/kg bolus followed by 20 mg/kg infusion over 1 h) administered in addition to a colloid resuscitation regimen. Female Large White pigs (45–60 kg) were bled 40% of their blood volume and peritonitis was induced using E. coli (O18: K1: H7) in an autoclaved faecal suspension. Animals were resuscitated with either colloid alone ( n=5) or colloid plus pentoxifylline ( n=5). Pentoxifylline attenuated increases in mean arterial and pulmonary artery pressures and reduced both systemic and pulmonary vascular resistance. It worsened the lactic acidosis associated with ‘septic shock’ and failed to reduce serum TNF-α levels. Pentoxifylline, in the high doses used in this study, does not have a role as an adjunct to resuscitation in this clinically relevant model of trauma.