Showing papers on "Resuscitation published in 1995"

The Medical Emergency Team.

Abstract: The concept of a Medical Emergency Team was developed in order to rapidly identify and manage seriously ill patients at risk of cardiopulmonary arrest and other high-risk conditions The aim of this study was to describe the utilization and outcome of Medical Emergency Team interventions over a one-year period at a teaching hospital in South Western Sydney Data was collected prospectively using a standardized form Cardiopulmonary resuscitation occurred in 148/522 (28%) calls Alerting the team using the specific condition criteria occurred in 253/522 (48%) calls and on physiological/pathological abnormality criteria in 121/522 (23%) calls Survival rate to hospital discharge following cardiopulmonary arrest was low (29%), compared with other medical emergencies (76%)

Epinephrine Increases the Severity of Postresuscitation Myocardial Dysfunction

Abstract: Background Epinephrine has been the mainstay for cardiac resuscitation for more than 30 years. Its vasopressor effect by which it increases coronary perfusion pressure is likely to favor initial resuscitation. Its β-adrenergic action, however, may have detrimental effects on postresuscitation myocardial function when administered before resuscitation because it increases myocardial oxygen consumption. In the present study, our focus was on postresuscitation effects of epinephrine when this adrenergic agent was administered during cardiopulmonary resuscitation. Postresuscitation myocardial functions were compared with those of a selective α-adrenergic agent, phenylephrine, when epinephrine was combined with a β1-adrenergic blocking agent, esmolol, and saline placebo. Methods and Results Ventricular fibrillation was induced in 40 Sprague-Dawley rats. Mechanical ventilation and precordial compression was initiated either 4 or 8 minutes after the start of ventricular fibrillation. The adrenergic drug or salin...

Cardiopulmonary resuscitation in the delivery room. Associated clinical events.

Abstract: Objectives: To determine (1) what percentage of infants require chest compressions and medications as part of resuscitation in the delivery room, (2) the associated clinical events contributing to neonatal depression, and (3) the neonatal outcome of such children. Design: Observational study. Setting: Urban county hospital. Results: For 2 years, 39 (0.12%) of 30 839 infants were administered chest compressions and/or epinephrine as part of cardiopulmonary resuscitation in the delivery room. Fifteen were term infants and 24 were premature. Five term infants had evidence of severe fetal acidemia (FA) (umbilical cord arterial pH P Conclusions: Cardiopulmonary resuscitation in the delivery room, resulting in administration of chest compressions and medications, is a rare event. Approximately one third of the infants had evidence of severe FA; in the remaining two thirds, ineffective or improper initial ventilatory support was the presumed mechanism for the continued neonatal depression. The appropriate therapeutic response to continuing neonatal depression should be to optimize ventilatory support before administering chest compressions or medications. (Arch Pediatr Adolesc Med. 1995;149:20-25)

Prospective, randomized trial of survivor values of cardiac index, oxygen delivery, and oxygen consumption as resuscitation endpoints in severe trauma.

Abstract: The objective was to test prospectively supranormal values of cardiac index (CI), oxygen delivery index (DO2I), and oxygen consumption index (VO2I) as resuscitation goals to improve outcome in severely traumatized patients. We included patients > or = 16 years of age who had either (1) an estimated blood loss > or = 2000 mL or (2) a pelvic fracture and/or two or more major long bone fractures with > or = four units of packed red cells given within six hours of admission. The protocol resuscitation goals were CI > or = 4.5 L/min/m2, DO2I > or = 670 mL/min/m2, and VO2I > or = 166 mL/min/m2 within 24 hours of admission. The control resuscitation goals were normal vital signs, urine output, and central venous pressure. The 50 protocol patients had a significantly lower mortality (9 of 50, 18% vs. 24 of 65, 37%) and fewer organ failures per patient (0.74 +/- 0.28 vs. 1.62 +/- 0.45) than did the 75 control patients. We conclude that increased CI, DO2I, and VO2I seen in survivors of severe trauma are primary compensations that have survival value; augmentation of these compensations compared to conventional therapy decreases mortality.

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

Abstract: 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.

Hypertonic sodium resuscitation is associated with renal failure and death.

Abstract: Objective The use of hypertonic sodium solutions (HSS) and lactated Ringer's (LR) solution in the resuscitation of patients with major burns was compared. Summary Background Data Hypertonic sodium solutions have been recommended for burn resuscitation to reduce the large total volumes required with isotonic LR solution and their attendant complications. Methods To evaluate the efficacy of this therapy in our adult burn center, we resuscitated 65 consecutive patients with HSS (290 mEq/L Na) between July 1991 and June 1993 and compared them with 109 burn patients resuscitated with LR (130 mEq/L Na) between July 1986 and June 1988 (LR-1). A subsequent 39 patients were resuscitated with LR between September 1993 and August 1994 (LR-2). Results Patients receiving hypertonic sodium solutions versus LR-1 were similar with respect to age (46.0 vs. 43.6 years), total burn size (39.2% vs. 39.9%), incidence of inhalation injury (41.5% vs. 47.7%), and predicted mortality (34.6% vs. 30.2%). Total resuscitation volumes during the first 24 hours were lower among patients treated with HSS than those in the LR-1 group (3.9 ± 0.3 vs. 5.3 ± 0.2 mL/kg/%body surface area [BSA], p < 0.05). After 48 hours, however, cumulative fluid loads were similar (6.6 ± 0.6 vs. 7.5 ± 0.3 mL/kg/%BSA), and total sodium load was greater with the HSS group (1.3 ± 0.1 vs. 0.9 ± 0.1 mEq/kg/%BSA, p < 0.002). During the first 3 days after burn, serum sodium concentrations were moderately elevated in the HSS patients (153 ± 2 vs. 135 ± 1 mEq/L, p < 0.001). Patients resuscitated with HSS had a fourfold increase in renal failure (40.0 vs. 10.1%, p < 0.001) and twice the mortality of LR-1 patients (53.8 vs. 26.6%, p < 0.001). In patients resuscitated with HSS, renal failure was an independent risk factor (p < 0.001, by logistic regression). Analysis of these results prompted a return to LR resuscitation (LR-2). Age (41.6 ± 2.9 years), burn size (37.8 ± 3.9 %BSA), and incidence of inhalation injury (51.3%) were similar to the earlier groups. Total sodium load was less among LR-2 patients than the HSS group (0.7 ± 0.1 mEq/kg/%BSA, p < 0.01), but similar to the LR-1 patients. Renal failure developed in only 15.4%, and 33.3% died, similar to the LR-1 group and significantly lower than patients treated with HSS (p < 0.001 and p < 0.05, respectively). Conclusion Hypertonic sodium solution resuscitation of burn patients did not reduce the total resuscitation volume required. Furthermore, it was associated with an increased incidence of renal failure and death. The use of HSS for burn resuscitation may be ill advised.

The Medical Emergency Team: a new strategy to identify and intervene in high-risk patients

Abstract: Objective: To describe the utilisation of an emergency team that employs standardised calling criteria to facilitate the early identification and resuscitation of patients who are at risk of cardio...

Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analyses from the brain resuscitation clinical trials. The Brain Resuscitation Clinical Trial I and II Study Groups.

Abstract: Objective To assess survival after cardiac arrest and to determine whether age is an independent determinant of late mortality or poor neurologic outcome. Design Analyses using results of Brain Resuscitation Clinical Trial I (1979 to 1984) and Brain Resuscitation Clinical Trial II (1984 to 1989), two randomized, double-blind studies of outcome following cardiac arrest. Setting A multicenter study in 12 acute care hospitals in nine countries (Brain Resuscitation Clinical Trial I), and 24 hospitals in eight countries (Brain Resuscitation Clinical Trial II). Patients A total of 774 patients who were initially comatose after successful resuscitation from cardiac arrest. The analyses include both in- and out-of-hospital cardiac arrests. Results The 6-month mortality rate for the entire group was 81%. Mortality rate was 94% for the oldest group (more than 80 yrs) compared with 68% for the youngest group (less than equals 45 yrs) (p less than .01). Other independent predictors of mortality were history of diabetes mellitus, inhospital arrests, arrest time of more than 5 mins, history of congestive heart failure, a noncardiac cause of arrest, and cardiopulmonary resuscitation time of more than 20 mins. Of the 774 patients, 27% recovered good neurologic function. There was no statistically significant difference in neurologic recovery rates by age. Multivariate analysis showed that independent predictors of good neurologic recovery were: no history of diabetes mellitus, a cardiac cause of arrest, short arrest time, and short cardiopulmonary resuscitation time. Conclusion Increasing age was a factor in postresuscitation mortality, but was not an independent predictor of poor neurologic outcome.

Preferences for cardiopulmonary resuscitation - Physician-patient agreement and hospital resource use

Abstract: OBJECTIVE: To describe the association between hospital resource utilization and physicians’ knowledge of patient preferences for cardiopulmonary resuscitation (CPR) among seriously ill hospitalized adult patients.

Gastric mucosal pH and oxygen delivery and oxygen consumption indices in the assessment of adequacy of resuscitation after trauma: a prospective, randomized study.

Abstract: Objective : To compare gastric mucosal pH (pHi) and global oxygen variables [Oxygen Delivery Index (DO 2 I) and Oxygen Consumption Index (VO 2 I)] as indicators of adequacy of resuscitation after major trauma. Methods : Twenty-seven patients were prospectively randomized into two groups : group 1 (n = 11), normalization and maintenance of pHi at or above 7.30 ; and group 2 (n = 16), maintaining a DO 2 I of 600 and a VO 2 I of >150. The groups had statistically similar injury severity scores, lactate, and base deficit. Results : The goals of therapy were achieved within 24 hours of admission in 10 of the 11 patients in group 1 and in 15 of the 16 patients in group 2. One patient (9.1%) in group 1 died. This patient had transient stabilization of pHi to 7.3 and subsequently had persistent mucosal acidosis. Of the 10 patients with pHi > 7.3 at 24 hours, 9 survived. In group 2, 5 (31.3%) died. Four of the 5 nonsurvivors had achieved DO 2 I and VO 2 I goals, but had pHi < 7.3 at 24 hours. A comparison of time taken for optimization of DO 2 I, VO 2 I, lactate, base excess, and pHi showed pHi and lactate as the variables different in survivors and nonsurvivors. Six of the 8 patients who developed multiple organ dysfunction syndrome had pHi < 7.3 at 24 hours. Persistently low pHi was the first sign of bacteremia (3 patients), small bowel gangrene or pregangrene (2 patients), intestinal anastomotic leak (2 patients), intra-abdominal hypertension (4 patients), and intra-abdominal abscess (5 patients). It was the first finding in all the nonsurvivors at least 72 hours before death. Conclusions : pHi may be an important marker to assess the adequacy of resuscitation. pHi monitoring may provide early warning for systemic complications in the postresuscitation period.

No-reflow after cardiac arrest

Abstract: Successful resuscitation of the brain requires unimpaired blood recirculation. The study addresses the question of the severity and reversibility of no-reflow after cardiac arrest. Adult normothermic cats were submitted to 5, 15 and 30 min cardiac arrest by ventricular fibrillation. The extent of no-reflow was assessed in each cardiac arrest group after 5 min closed chest cardiac massage in combination with 0.2 mg/kg epinephrine or after successful resuscitation followed by 30 min recirculation. Reperfusion of the brain was visualized by labelling the circulating blood with FITC-Albumin. Areas of no-reflow, defined as absence of microvascular filling, were identified by fluorescence microscopy at 8 standard coronal levels of forebrain, and expressed as percent of total sectional area. During cardiac massage, noreflow affected 21±5%, 42±38% and 70±27% of forebrain after 5, 15 and 30 min cardiac arrest, respectively. After 30 min spontaneous recirculation following successful resuscitation of the heart, no-reflow significantly declined to 7±11% after 5 min cardiac arrest (p<0.05) but persisted in 30±11% and 65±21% of forebrain after 15 and 30 min cardiac arrest, respectively (n.s.). Our observations demonstrate that resuscitation of the heart by closed chest massage causes severe (and after prolonged cardiac arrest irreversible) no-reflow of the brain. This suggests that no-reflow is an important cause of postresuscitation brain pathology.

Association of Drug Therapy with Survival in Cardiac Arrest: Limited Role of Advanced Cardiac Life Support Drugs

Abstract: Objective: To generate hypotheses regarding the association of standard Advanced Cardiac Life Support (ACLS) drugs with human cardiac arrest survival. Methods: This observational cohort study was conducted over a two-year period in the wards, intensive care units, and EDs of two tertiary care hospitals. Included were adult patients who suffered cardiac arrest either inside or outside the hospital and who required epinephrine according to standard ACLS guidelines. Six standard ACLS drugs (given while CPR was in progress) were assessed for association with survival from resuscitation to one hour and to hospital discharge by univariate and multivariate logistic regression analyses. Results: In the 529 patients studied, initial cardiac rhythm had no impact on the association between drug administration and survival. The time of drug administration (quartile of ACLS period) was associated with resuscitation for atropine (p < 0.05) and lidocaine (p < 0.01). The odds ratios (95% CIs) for successful resuscitation, after multivariate adjustment for potential confounders, were: a respiratory initiating cause, 3.7 (2.1–6.4); each 5-minute increase in CPR-ACLS interval, 0.5 (0.4–0.7); each 5-minute duration of ACLS, 0.9 (0.8–1.0); atropine, 1.2 (1.0–1.3); bretylium, 0.4 (0.1–1.1); calcium, 0.8 (0.2–2.4); lidocaine, 0.9 (0.7–1.1); procainamide, 21.0 (5.2–84.0); and sodium bicarbonate 1.2 (1.0–1.6). All other potential confounding variables entered into the model were not significantly associated with resuscitation. Conclusion: Initiating cause of arrest, time to ACLS, and duration of ACLS were important correlates of survival. Other than procainamide, standard ACLS drugs had relatively little association with survival, but timing of administration may be an important factor. Further research using definitive large randomized controlled trials is warranted to assess the role of drug therapy in improving cardiac arrest survival.

Surrogates' predictions of seriously ill patients' resuscitation preferences.

Abstract: Background Seriously or terminally ill patients are frequently incapacitated and unable to express their preferences regarding cardiopulmonary resuscitation (CPR). In this situation, family members or other surrogate decision makers are often asked whether they believe the patient would want to be resuscitated. We evaluated the concordance of patient CPR preferences and surrogate perceptions of the patient preferences in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), a large, multicenter study of seriously ill hospitalized patients. Methods We compared patient preferences and surrogate perceptions in 1226 pairings in which both patient and surrogate responded to CPR decision questions. We also examined factors that might influence patient-surrogate concordance. Results Twenty-nine percent of patients with paired data did not want to be resuscitated; 26% of surrogates did not believe the patient they represented would want to be resuscitated. Within pairs, the overall exact agreement with respect to CPR decisions was 74%. For patients favoring CPR, only 16% of the surrogates misconstrued the patient's wishes. For patients who did not want to be resuscitated, however, 50% of the surrogates did not reflect the patient's wishes. If patients reported telling surrogates their CPR preference, concordance was significantly improved if the surrogate believed the patient did not want to be resuscitated and was significantly worsened if the surrogate believed the patient wanted CPR. This finding is likely an artifact of patients being more likely to report their preference to surrogates if that preference was not to be resuscitated. Conclusions Surrogates' perceptions of patient CPR preferences are often inaccurate, particularly for those patients who do not want to be resuscitated. Methods to improve communication between patients and surrogates on CPR preferences should be developed and evaluated.

Outcome and cost at a children's hospital following resuscitation for out-of-hospital cardiopulmonary arrest

Abstract: Objective: To determine the outcome and cost for children resuscitated following out-of-hospital cardiopulmonary arrest. Design: Retrospective case series. Setting: An organized prehospital emergency medical system within Birmingham, Ala, in a county with 150 493 children under the age of 15 years. Patients: Sixty-three pediatric victims of out-of-hospital cardiopulmonary arrest of any cause presenting to the emergency department of a children's hospital. Intervention: Standard resuscitative techniques were performed for all patients until resuscitative efforts were discontinued in the hospital emergency department or successful resuscitation was achieved. Main Outcome Measures: Successful resuscitation, survival to hospital discharge, neurological outcome, final disposition, and cost of hospital care. Results: Of 63 children with out-of-hospital cardiopulmonary arrest treated in the emergency department of a children's hospital, 60 were pulseless and apneic on arrival, 18 (28.6%) were successfully resuscitated and admitted to the intensive care unit, and six (9.5%) were discharged from the hospital. Five of the survivors had severe neurological deficits and one appeared normal. On follow-up, two patients had died (1 month and 7 months after discharge), three were in a vegetative state, and one was normal. The normal patient had successful defibrillation prior to arrival at the emergency department. The average inpatient charge was $10 667 per patient for those who died and $100 000 for those discharged. Conclusions: Aggressive treatment does not lead to intact survival for victims of out-of-hospital cardiopulmonary arrest who present to the pediatric emergency department with a preterminal rhythm and absence of spontaneous circulation. Resuscitation efforts in the emergency department are commonly successful but lead to death or severe neurological sequelae at discharge with extremely high cost of care. (Arch Pediatr Adolesc Med. 1995;149:210-214)

The cardiopulmonary resuscitation-not-indicated order: futility revisited.

Abstract: This paper reviews the advent of unilateral do-not-resuscitate orders. Unilateral do-not-resuscitate policies presume that cardiopulmonary resuscitation is a medical therapy and that physicians hav...

Outcome of a Strict Policy on Emergency Department Thoracotomies

Abstract: Objective: To audit emergency department thoracotomies from January 1981 to May 1993. Design: Retrospective analysis of case records. Setting: A large (3000-bed) tertiary care academic hospital; the department of general surgery (including trauma) consists of 360 beds. Patients: All patients who underwent a thoracotomy in the emergency department during the above period. Intervention: An emergency department thoracotomy was performed on trauma patients with recordable vital signs and rapid deterioration and on patients with uncontrollable bleeding or profound hypotension not responsive to resuscitation. The procedure was performed either on the resuscitation trolley in the emergency department or in the adjacent operating room. Main Outcome Measures: Survival and subsequent neurological function after thoracotomy. Results: There were 312 stab injuries, 358 gunshot injuries, and 176 blunt injuries. Survival occurred in 26 stab-wound cases (8.3%), in 16 gunshot cases (4.4%), and in one blunt injury case (0.6%). There was one patient with neurological impairment in each of the three injury groups. Those with penetrating chest injuries had the best survival rate (20%), and the survival rate for penetrating abdominal trauma was 6.8%. Conclusions: Emergency department thoracotomies have a definite role in the management of trauma patients. The best results are obtained in patients with penetrating chest injuries. (Arch Surg. 1995;130:774-777)

Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

Abstract: Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

Multiple Resuscitation Regimens in a Near‐fatal Porcine Aortic Injury Hemorrhage Model

Abstract: 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.

Extracorporeal cardiopulmonary life support with heparin-bonded circuitry in the resuscitation of massively injured trauma patients*

Abstract: Background Patients who have massive but potentially survivable injuries frequently die from complications of hypovolemia, hypoxemia, hypothermia, metabolic acidosis, and coagulopathy. Emergency cardiopuhnonary bypass has been unsuccessful in preventing such deaths because it involves systemic anticoagulation that exacerbates coagulopathy. Patients and methods A simplified extracorporeal cardiopuhnonary life support (ECLS) system was assembled consisting of a centrifugal pump head, heat exchanger, membranous oxygenator, percutaneous cannulas, and heparin-bonded circuitry. The entire system has heparin-bonded surfaces. Patients were resuscitated with the system after femoral vein-femoral artery cannulation. ECLS was used to resuscitate massively injured patients who were deteriorating despite maximal conventional therapy. Results While receiving maximal conventional therapy, 6 patients developed hypothermia, metabolic acidosis, and coagulopathy causing pulmonary hemorrhaging and hypoxemia from severe underlying lung injuries. ECLS with heparin-bonded circuitry provided cardiopulmonary support and rewarming while physicians addressed coagulopathies and surgical bleeding and assessed survivability. Three patients survived. Conclusions ECLS with heparin-bonded circuitry offers supplemental capability in the resuscitation and cardiopuhnonary support of selected massively injured patients while their primary injuries are being evaluated and treated.

Pathogenesis of hemorrhage-induced bacteria/endotoxin translocation in rats. Effects of recombinant bactericidal/permeability-increasing protein.

Abstract: OBJECTIVES: This study was conducted to determine the role of gut-derived bacteria/endotoxin in the pathogenesis of the multiple-organ damage and mortality, the possible beneficial effect of recombinant bactericidal/permeability-increasing protein (rBPl21), and whether neutralizing endotoxemia by rBPl21 treatment influences tumor necrosis factor (TNF) formation in rats after hemorrhagic shock and resuscitation. SUMMARY BACKGROUND DATA: Hypovolemic shock might be associated with bacterial or endotoxin translocation as well as systemic sepsis. Similar to bactericidal/permeability-increasing (BPl) protein, rBPl21 has been found to bind endotoxin and inhibit TNF production. METHODS: A rat model of prolonged hemorrhagic shock (30 to 35 mm Hg for 180 min) followed by adequate resuscitation was employed. Recombinant bactericidal/permeability-increasing protein was administered at 5 mg/kg intravenously. The control group was treated similarly to the BPl group, but received thaumatin as a protein-control preparation in the same dose as rBPl21. RESULTS: Immediately after resuscitation (230 min), plasma endotoxin levels in the control group (61.0 +/- 16.3 pg/mL) were almost neutralized by rBPl21 treatment (13.8 +/- 4.8 pg/mL, p < 0.05). Plasma TNF levels were not significantly influenced by rBPl21 treatment. The 48-hour survival rate was 68.8% in the treatment group versus 37.5% in the control group (p = 0.08). Microscopic histopathologic examination revealed relatively minor damage to various organs in the treatment group. CONCLUSIONS: These data suggest that hemorrhagic shock may lead to bacterial/endotoxin translocation with concomitant TNF formation, endogenous endotoxemia may play an important role in the pathogenesis of multiple-organ failure after shock and trauma, TNF formation at an early stage might be related mainly to mechanisms other than Kupffer's cells activation via lipopolysaccharide, and rBPl21 might be a useful therapeutic agent against endogenous bacteria/endotoxin related disorders in severe hemorrhagic shock.