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Gender differences in 24-hour outcome following resuscitation after 9 minutes of cardiac arrest in dogs.

OBJECTIVE: To examine possible gender-specific differences in 24-hr outcome following resuscitation from 9 mins of controlled cardiac arrest. DESIGN: Preclinical, prospective study comparing two similarly prepared, independent control groups (one female group, one male group) included in a larger series of studies. SETTING: Physiology research laboratory at a major medical center. SUBJECTS: Male and female mongrel dogs (Canis familiaris), weighing 16 to 22 kg. INTERVENTIONS: Cardiopulmonary-cerebral resuscitation following 9 mins of normothermic cardiac arrest in male vs. female dogs. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure, heart rate, urine output, arterial blood oxygen, and PCO2 values, arterial pH, temperature, plasma glucose concentrations, and hematocrit were measured and recorded at the precardiac arrest and postcardiac arrest period, and at 30 mins, and 1, 4, 6, 12, and 24 hrs following resuscitation. Neurologic dysfunction was assessed using a well-standardized neurologic deficit score assigned at 6, 12, and 24 hrs after arrest. Plasma concentrations of malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced glutathione were measured at the precardiac arrest period, and 6, 12, and 24 hrs following resuscitation. Additionally, serum concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase, gamma-glutamyl transferase, creatinine kinase, creatinine, albumin, and total protein were measured before arrest, and at 6, 12, and 24 hrs after resuscitation. Plasma concentrations of inorganic phosphorus, blood urea nitrogen, and electrolytes (sodium, chloride, calcium, and potassium) were measured. The estrous cycle phase in the female dogs enrolled in the study was determined by physical examination and vaginal cytology. No prearrest differences were detectable between males and females in basic physiologic variables. No differences in neurologic deficit were detectable between males and females across the 24-hr recovery period following resuscitation. No detectable differences in malonaldehyde, 4-hydroxynonenal, and erythrocyte-reduced glutathione occurred between groups. Serum concentrations of aspartate aminotransferase (p = .02), alanine aminotransferase (p = .009), creatinine kinase (p = .01), total bilirubin (p = .05), and plasma concentrations of inorganic phosphorus (p = .03), blood urea nitrogen (p = .0003), and creatinine (p = .02) all were significantly and dramatically higher in female than male dogs at the 24-hr time point. The trend of increase in these values began at the 6- and 12-hr time points and was consistent with a steadily decreasing trend in mean arterial pressure and an increasing trend in heart rate in the female group. CONCLUSIONS: An extensive history with this preclinical canine model (restricted to male dogs) had indicated little or no change in standard clinical chemistry markers of systemic dysfunction following 9 mins of cardiac arrest. However, when compared with male dogs, the female dogs tested here appear to have sustained a more significant hepatic and renal ischemic injury with no differences in the neurologic deficit.

Alanine Transaminase↗

Marked activation of complement and leukocytes and an increase in the concentrations of soluble endothelial adhesion molecules during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans.

OBJECTIVE: Animal studies have demonstrated that reperfusion disorders occurring after cardiac arrest affect outcome. Reperfusion injury can be caused by activation of complement, polymorphonuclear leukocytes (PMN), and PMN-endothelial interaction. We studied different specific markers of these processes during and after cardiopulmonary resuscitation in humans. DESIGN: Prospective clinical trial. SETTING: University hospital. PATIENTS: A total of 55 patients who underwent out-of-hospital cardiopulmonary resuscitation for nontraumatic causes. INTERVENTIONS: Blood samples were drawn immediately, 15 mins, and 30 mins after initiation of cardiopulmonary resuscitation. In the case of restoration of spontaneous circulation, additional blood samples were taken at serial time points until 7 days after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: A marked activation of complement and PMN was found in all patients investigated. Serum concentrations of specific activation markers of the complement system, anaphylatoxin C3a and the soluble membrane attack complex SC5b-9, and PMN elastase were increased during cardiopulmonary resuscitation and for </=48 hrs after restoration of spontaneous circulation. Compared with controls at 30 mins after initiation of cardiac massage, concentrations of C3a, SC5b-9, and PMN elastase were increased in patients without and in those with restoration of spontaneous circulation. PMN elastase concentrations were significantly greater in patients without restoration of spontaneous circulation than in those who could be stabilized. In addition, the plasma concentrations of the soluble P-selectin were significantly increased between 15 mins and 24 hrs after the start of cardiopulmonary resuscitation. The concentrations of soluble intercellular adhesion molecule-1 were increased between 2 hrs and 72 hrs. CONCLUSIONS: Our data clearly demonstrate a marked activation of complement and PMN and an increased PMN-endothelial interaction during cardiopulmonary resuscitation and early reperfusion after cardiac arrest in humans. These changes are known to induce reperfusion disorders and tissue injury and point to new therapeutic options to improve outcome after cardiac arrest.

Aged↗

Resuscitation of thermally injured patients with oxygen transport criteria as goals of therapy.

Resuscitation from shock based on oxygen transport criteria has been widely used in trauma and surgical patients, but has not been examined in thermally injured patients. To study the possible efficacy of this type of resuscitation, the oxygen transport characteristics of burn resuscitation were studied in nine adults, of whom six had inhalation injuries, with a mean burn size of 45% total body surface area and a mean age of 33.4 years, who were resuscitated based on oxygen transport criteria. Pulmonary artery balloon flotation catheters were placed and hemodynamic and oxygen transport parameters (Fick method) were measured hourly for 6 hours. Patients received fluid boluses in addition to resuscitation calculated by the Parkland formula, until the pulmonary artery wedge pressure reached 15 mm Hg, after which dobutamine infusions (5 micrograms/kg/min) were initiated. Cardiac index increased from 2.51 to 6.57 L/min/m2 (p < 0.05), whereas systemic vascular resistance fell from 1534 to 584 dyne sec/cm5 (p < 0.05). Oxygen delivery (DO2I) and oxygen consumption (VO2I) indexes increased significantly during the study period (573 +/- 47 to 1028 +/- 57, and 132 +/- 8 to 172 +/- 16 ml/min/m2, respectively; p < 0.05). VO2I appeared dependent on DO2I at levels of DO2I less than 800 ml/min/m2. In this study, depressed cardiovascular function in patients with burn injuries responded to volume loading and inotropic support much as it does in patients with shock of other etiologies. Whether oxygen transport-based resuscitation is effective in improving survival or the incidence of multiple organ failure is unknown and will need to be evaluated in randomized trials.

Adult↗

Acute respiratory failure that complicates the resuscitation of pediatric patients with scald injuries.

Respiratory failure that requires endotracheal intubation is an uncommon but potentially fatal complication of scald burns in children. Because scalds are rarely associated with a direct pulmonary injury, the pathophysiology of respiratory failure is unclear. A possible mechanism may be upper airway edema, diminished pulmonary compliance secondary to fluid resuscitation, or both. To identify an at-risk population for intubation after a scald injury, the hospital courses of 174 consecutive patients under the age of 14 years who were admitted after a scald injury to a single burn center during a 6-year period were examined. Seven of these patients (4%) required endotracheal intubation. No patient older than 2.8 years or who had a scald injury that covered less than 19% of the total body surface area required intubation. Patients who required intubation were younger (mean age, 1.4 vs. 2.8 years, P<.001), had a larger mean burn size (29.9% vs. 12.3% total body surface area, P<.001), and required more fluid resuscitation (7.66 vs. 4.07 cc/kg per percentage of total body surface area burned, P<.001) than patients who did not require intubation. Examination of the adequacy of resuscitation revealed that the intubated patients had an average hourly urine output of 0.84 cc/kg during the first 24 hours, suggesting that resuscitation was not excessive. Multivariate analysis demonstrated that both larger burn size (P = .041) and younger age (P = .049) were independent predictors of the need for intubation. Young patients with large body surface area burns that required large volumes of resuscitation comprise an at-risk group for respiratory failure after a scald injury. Increased vigilance is merited during the resuscitation of these patients.

Adolescent↗

The beneficial role of calcium supplementation during resuscitation from shock.

The role of calcium (Ca) in resuscitation from hemorrhagic shock is controversial and in the present report three regimens were compared: supplementation (Ca-S), avoidance (No-Ca), and Ca channel blockade (Ca-B). This was studied in 40 splenectomized dogs subjected to reservoir shock (MAP 60 torr/90 min, then 40 torr/30 min) and treated with: a) 20 ml/kg balanced electrolyte solution (BES); b) shed blood; c) 30 ml/kg BES; and d) 250 ml autologous bank blood. Three groups of six dogs received Ca-S (0.5 mEq/kg), No-Ca, or Ca-B (verapamil 0.15 mg/kg) in BES. Postoperative therapy of 50 ml/kg/d BES with Ca-S, No-Ca, or Ca-B was given for 3 days. The effects of parathyroidectomy (P) via wide thyroidectomy in 22 dogs treated with calphosan (20 ml/d) and L-thyroxin (0.02 mg/kg) preceding shock was also studied as above: Ca-S/P, No-Ca/P, and Ca-B/P; four sham dogs had anesthesia but no shock (Anes/P). Studies done before, during, and after shock and on day three included systemic pressures (MAP), central pressures (CFP), cardiac output (CO), resistance (SVR), heart work (LVW), and outcome. Post-resuscitation Ca was significantly less in all groups (1.6-3.7 mg%) compared to Ca-S (4.8 mg%). Compared to Ca-S dogs, the post-resuscitation studies in the No-Ca and Ca-B dogs showed lower MAP, CO, and LVW in both intact and hypoparathyroid animals. Post-resuscitation CFP was also lower in the Ca-S and Ca-S/P dogs compared to the other euparathyroid and hypoparathyroid dogs. Death after the initiation of resuscitation occurred in two No-Ca/P and three Ca-B/P dogs. These data suggest that calcium supplementation plus an intact calcium-parathyroid axis enhance the resuscitation effort.

Animals↗

Effects of resuscitation from hemorrhagic shock on cerebral hemodynamics in the presence of an intracranial mass.

This study compares intracranial pressure, cerebral blood flow, and cerebral oxygen transport during hemorrhagic shock and following fluid resuscitation with crystalloid or colloid solution in a canine model with an epidural mass lesion. After placement of an epidural balloon, intracranial pressure was increased to 30 mm Hg for 5 minutes and then permitted to vary without further manipulation. Hemorrhagic shock was produced by the rapid removal of blood to achieve a mean arterial pressure of 55 mm Hg for 30 minutes. Resuscitation then was performed with intravenous lactated Ringer's solution, 60 ml/kg, or with 6.0% hetastarch, 20 ml/kg. Following both solutions mean arterial pressure and cardiac output were increased and hemoglobin concentration was reduced. Intracranial pressure was significantly lower immediately after resuscitation in the hetastarch group; it then gradually increased so that the difference was much less 1 hour later. Cerebral blood flow decreased during shock and was not restored by either fluid; cerebral oxygen transport fell further with resuscitation in both groups due to hemodilutional reductions in hemoglobin. Although colloid resuscitation improved systemic hemodynamics and maintained lower intracranial pressure, it failed, as did crystalloid resuscitation, to restore cerebral oxygen transport to prehemorrhagic shock levels.

Animals↗

Effects of hypertonic and isotonic fluid infusion on the flash evoked potential in rats: hemorrhage, resuscitation, and hypernatremia.

In resuscitation from hemorrhagic shock, very small volumes of hypertonic saline (HS) improve blood pressure while reducing intracranial pressure and edema formation. The effects of hypertonic resuscitation fluids and hypernatremia on electrophysiologic brain function have not been studied. The present study was done in two parts. First we examined the effects of hemorrhagic shock and resuscitation with either 7.5% HS or lactated Ringer's (LR) solution on the flash evoked potential (FEP). Rats were bled to a mean arterial pressure (MAP) of 35 mm Hg for 1 hour, then resuscitated with HS (n = 10) or LR (n = 10) to a MAP of 80 mm Hg for another hour. Resuscitation required 3.8 +/- 0.5 mL/kg HS and 42.9 +/- 7.5 mL/kg LR (p < 0.05). During hemorrhage, FEP latencies increased and amplitudes decreased. During resuscitation, these variables returned toward baseline values. There were no significant differences between groups, although HS tended to restore the FEP better than LR. We next examined the effects on the FEP of hypernatremia and hyperosmolarity produced by two different hyperosmotic fluids. Over a 1-hour period, 16 mL/kg HS (n = 8), 16 mL/kg IsoSal (4.5% saline, 5.9% glucose, 6.4% mixed amino acids; n = 8), or 40 mL/kg LR (n = 8) was infused into normovolemic rats. Plasma sodium levels increased in both hyperosmotic groups (baseline = 145.2 +/- 0.7 mEq/L; after infusion, HS = 202.4 +/- 9.8 mEq/L, IsoSal = 163.3 +/- 4.2 mEq/L; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The relationship of base deficit to lactate in porcine hemorrhagic shock and resuscitation.

This study was undertaken to determine the relationship of arterial and venous base deficit (BD) to lactate levels and SvO2 in shock and resuscitation with the hypothesis that BD is an equally good indicator of the physiologic changes while being more readily accessible. Fifteen mature swine were bled serially of 25% and 40% of their calculated blood volumes, then resuscitated with lactated Ringer's and blood. Serial hemodynamic and metabolic measurements were made. The BD correlated significantly with lactate levels at all increments of shock and resuscitation. Linear regression analysis demonstrated strong associations (p < 0.001) for arterial and venous BD (R = 0.808), for BD and lactate (R = -0.794), and BD and SvO2 (R = 0.538). The BD accurately reflected the hemodynamic and tissue perfusion changes associated with hemorrhagic shock and resuscitation. Base deficit is more readily available than lactate, and is therefore more useful as an index of shock and resuscitation. Venous BD correlates well with arterial BD and can be used when an arterial sample cannot be obtained. The SvO2 correlated well with acute volume changes but the addition of supplemental oxygen made it a less reliable indicator of hemorrhage and resuscitation.

Acidosis↗

Cardiac preload, splanchnic perfusion, and their relationship during resuscitation in trauma patients.

INTRODUCTION: Low gastric intramucosal pH (pHi) after shock resuscitation is associated with organ dysfunction and death in trauma patients. However, the relationship between hemodynamic performance, global oxygen transport, and pHi is unclear. Our purpose was to evaluate the relationship between intravascular volume status, splanchnic hypoperfusion, and outcome after shock resuscitation in trauma patients. DESIGN/SETTING: Cohort study of 79 consecutive critically ill patients at a Level I trauma center stratified by normal (NORM, > or = 7.32) or low (LOW, < 7.32) pHi when lactate normalized (< 2.2 mmol/L). MAIN OUTCOME MEASURES: Differences during resuscitation in mean values of right ventricular end-diastolic volume index (RVEDVI), pulmonary artery occlusion pressure, cardiac index, oxygen delivery index, and oxygen consumption index. The incidence of multiple organ failure and death in the NORM and LOW groups were analyzed via odds ratio and chi 2. RESULTS: Patients in the NORM group (n = 45) had a lower incidence of multiple organ failure (4 of 45 vs. 11 of 34, odds ratio 5.0, p < 0.01) and death (5 of 45 vs. 11 of 34, odds ratio 3.8, p < 0.05) than patients in the LOW group (n = 34). NORM patients had a higher initial RVEDVI (116 +/- 31 vs. 95 +/- 25 mL/m2, p < 0.001) and maintained a significantly higher RVEDVI (114 +/- 27 vs. 97 +/- 17 mL/m2, p = 0.003) throughout resuscitation than the LOW group did. There were no differences in the other studied variables. CONCLUSIONS: Supranormal levels of preload during shock resuscitation are associated with better outcome. Maintaining a RVEDVI higher than 100 mL/m2 during shock resuscitation may be of benefit in critically injured patients.

Adult↗

Initial small-volume hypertonic resuscitation of shock and brain injury: short- and long-term effects.

BACKGROUND: Initial small-volume hypertonic saline resuscitation of a combined hemorrhagic shock and head injury model was studied. METHODS: Twenty-three sheep underwent hemorrhage (20 mL/kg) and parietal freeze injury followed by initial bolus resuscitation with lactated Ringer's solution (40 mL/kg) or 7.5% hypertonic saline (HS) (4 mL/kg). Cardiac index was maintained with lactated Ringer's solution for either 2 or 24 hours. Parietal lobe water content, blood volume, and blood flow were determined. Intracranial pressure (millimeters of mercury) was followed. RESULTS: Overall fluid requirements (milliliters per kilogram) were less at 2 and 24 hours with HS resuscitation. Early intracranial pressure was less with HS resuscitation. Brain water contents were similar between groups. Blood flow in injured and blood volume in uninjured parietal lobe were less for HS at 2 hours, although not different at 24 hours. CONCLUSIONS: Less fluid was needed in the short- and long-term with HS resuscitation. Early intracranial pressure was higher with lactated Ringer's solution resuscitation, possibly in part owing to increased blood volume.

Animals↗

Use of tissue oxygen tension measurements during resuscitation from hemorrhagic shock.

BACKGROUND: Tissue oxygen tension can be measured directly in selected organ beds, and these measurements may be more sensitive in assessing the adequacy of resuscitation than global physiologic parameters. We hypothesized that heart tissue oxygen tension would be an important marker for the severity of ischemic insult to the heart during hemorrhagic shock. We further hypothesized that gut oxygen tension measured in the jejunum would prove to be a better measure of splanchnic hypoperfusion than intramucosal pH (pHi). METHODS: Tissue oxygen probes were inserted directly into the myocardium of the left ventricle and into the lumen of the proximal jejunum in 10 anesthetized swine. A pHi catheter was introduced into the stomach. The animals were subjected to a controlled hemorrhage of 50% of estimated blood volume. Gut and cardiac oxygen were monitored continuously during hemorrhage and resuscitation, which was performed with shed blood and crystalloid. RESULTS: While gut O2 and pHi trended together, we were unable to establish a correlation between changes in these two variables during hemorrhage and resuscitation. Heart PO2 decreased significantly during hemorrhage, but surpassed baseline values after resuscitation, a finding not seen in gut PO2. No standard physiologic variables reliably predicted changes in heart PO2 during these experiments. CONCLUSIONS: Tissue oxygen tensions measurements are highly responsive to changes induced during graded hemorrhagic shock and resuscitation. Gut PO2 and pHi appear to be measuring different physiologic processes in the gastrointestinal tract. The compensatory ability of the heart far exceeds that of the gut after ischemic insult. This hemorrhagic shock model appears feasible for the study of various methods of resuscitation.

Animals↗

Randomized, prospective comparison of increased preload versus inotropes in the resuscitation of trauma patients: effects on cardiopulmonary function and visceral perfusion.

OBJECTIVE: To evaluate the effects of maintaining increased levels of preload on cardiopulmonary function and visceral perfusion during resuscitation. METHODS: Randomized, prospective study of 39 consecutive trauma patients with a low right ventricular ejection fraction (<40%) admitted to a university Level I trauma center during a 10-month period. Patients were randomized to one of two groups: increased preload (PL), or normal preload with inotropes (INO). The PL group received fluid administration to maintain a target right ventricular end-diastolic volume index (RVEDVI) > or = 120 mL/m2 during resuscitation. The INO group had inotropes added according to a prospectively determined protocol and was maintained at a RVEDVI of 90 to 100 mL/m2. Systemic perfusion was assessed using oxygen transport and acid-base parameters, and pulmonary function was evaluated with PaO2/FiO2 ratio, dynamic compliance, ventilator days, and incidence of adult respiratory distress syndrome. Gut perfusion was assessed by measuring gastric intramucosal pH (pHi). Data are expressed as means +/- SD. RESULTS: The mean RVEDVI was significantly higher in the PL group (n = 19) than in the INO group (n = 20) during resuscitation (119+/-18 vs. 103+/-22 mL/m2, p = 0.01). There was no difference in oxygen delivery, mixed venous oxygen saturation, lactate, PaO2/FiO2 ratio, dynamic compliance, or ventilator days between the groups. The incidence of adult respiratory distress syndrome was not significantly different (PL 31% vs. INO 50%, p > 0.1). In the patients who had pHi measured sequentially during resuscitation (PL = 13, INO = 17), the final pHi was significantly higher in the PL group (7.31+/-0.1 vs. 7.16+/-0.2, p = 0.03). CONCLUSION: Patients resuscitated at higher levels of preload have significantly better visceral perfusion than those resuscitated at normal preload with addition of inotropes. This higher preload does not adversely affect pulmonary function.

Adult↗

Lactated Ringer's solution resuscitation causes neutrophil activation after hemorrhagic shock.

PURPOSE: To determine the degree of neutrophil activation caused by hemorrhagic shock and resuscitation. METHODS: Awake swine underwent 15-minute 40% blood volume hemorrhage, and a 1-hour shock period, followed by resuscitation with: group I, lactated Ringer's solution (LR); group II, shed blood; and group III, 7.5% hypertonic saline (HTS). Group IV underwent sham hemorrhage and LR infusion. Neutrophil activation was measured in whole blood using flow cytometry to detect intracellular superoxide burst activity. RESULTS: Neutrophil activation increased significantly immediately after hemorrhage, but it was greatest after resuscitation with LR (group I, 273 vs. 102%; p < 0.05). Animals that received shed blood (group II) and HTS (group III) had neutrophil activity return to baseline state after resuscitation. Group IV animals had an increase in neutrophil activation (259 vs. 129%; p < 0.05). CONCLUSION: Neutrophil activation occurring after LR resuscitation and LR infusion without hemorrhage, but not after resuscitation with shed blood or HTS, suggests that the neutrophil activation may be caused by LR and not by reperfusion.

Animals↗

Determining optimal cardiac preload during resuscitation using measurements of ventricular compliance.

BACKGROUND: While the right ventricular end-diastolic volume index (RVEDVI) has been shown to be a better indicator of preload than cardiac filling pressures, optimal values during resuscitation from trauma are unknown. This study examines right ventricular stiffness as a guide to optimal values of RVEDVI. METHODS: Prospective study of 19 critically injured patients monitored with a volumetric pulmonary artery catheter during resuscitation. Per resuscitation protocol, the target RVEDVI was > or = 120 mL/m2. Sequential fluid boluses of 500 to 1000 mL were administered to obtain at least four values of RVEDVI and right ventricular end-diastolic pressure (estimated by central venous pressure [CVP]). For each patient, nonlinear regression was used to construct the ventricular compliance curve based on the equation, CVP = aek(RVEDVI), where k is the coefficient of chamber stiffness. RESULTS: Overall, the derived compliance curves had excellent fit with the theoretical equation (mean R2, 0.95 +/- 0.04). Mean k was 0.043 +/- 0.012 (range, 0.029-0.067). For each patient, mean RVEDVI during resuscitation was significantly correlated with k (R2 = 0.75, p < 10-5) indicating that chamber stiffness, measured during initial fluid administration, may be used to determine RVEDVI during the ensuing resuscitation. CONCLUSION: In critically injured patients, bedside assessment of right ventricular compliance is possible and may help determine optimal values of RVEDVI during resuscitation.

Adult↗

Factors influencing termination of resuscitative efforts in children: a comparison of pediatric emergency medicine and adult emergency medicine physicians.

OBJECTIVES: To examine factors that influence termination of resuscitative efforts (TORE) and compare pediatric emergency medicine (PEM) and general emergency medicine (GEM) physicians regarding TORE in children. DESIGN: Cross-sectional survey. PARTICIPANTS: All physicians board-certified in PEM as of November 1993 and a random sample of board-certified GEM physicians listed in the 1993 American College of Emergency Physicians directory. INTERVENTIONS: Self-administered questionnaires were mailed to participants who were asked about experience providing pediatric cardiopulmonary resuscitation (CPR) and demographic information. We posed a series of management questions eliciting factors that influence TORE decision-making in single context and case scenario format. Specific emphasis was placed on the influence of time and epinephrine dosing. RESULTS: One hundred and sixty (70%) PEM and 127 (62%) GEM responded. These groups differed significantly in years of experience (PEM 8.2, GEM 11.8), urban practice setting (PEM 84%, GEM 32%) and number of pediatric cardiopulmonary resuscitations per year (PEM 10.6, GEM 4.8), P < 0.001 for all. There were no significant differences between groups regarding features pathognomonic of death. PEM were more likely to consider low blood pH and iatrogenic causes of arrest as factors influencing TORE; GEM were more likely to consider co-morbid conditions (P < 0.05 for all). Medians for time estimates of minimum minutes of pulselessness that influence TORE were: PEM 26 to 30 minutes, GEM 31 to 35 minutes for both prehospital and emergency department settings (P < 0.05 for each). Approximately 20% of all respondents did not place a strict limit on time of pulselessness when determining TORE. No difference was observed between groups regarding maximum doses of epinephrine used prior to TORE. However, fewer GEM (50%) than PEM (75%) utilize "high dose" epinephrine according to current Pediatric Advanced Life Support (PALS) guidelines (P < 0.05). PEM physicians were more than two times more likely to terminate resuscitative efforts if return of spontaneous circulation was not achieved by 25 minutes compared to GEM physicians for both prehospital time of pulselessness [odds ratio 2.1, 95% confidence interval (1.01, 4.5)] and emergency department time of pulselessness [odds ratio 2.2, confidence interval (1.1, 4.6)]. CONCLUSIONS: 1) Several laboratory and clinical factors significantly influence physician's decisions regarding TORE; 2) regardless of setting, time of pulselessness does appear to be an influential factor in determining when to terminate resuscitation in children for most physicians; 3) PEM physicians are more likely to terminate resuscitative efforts than are GEM physicians if return of spontaneous circulation is not achieved by 25 minutes; 4) a significant number of PEM and GEM physicians do not use high dose epinephrine in accordance with current PALS recommendations.

Adolescent↗

Effect of resuscitation with hydroxyethyl starch and lactated Ringers on macrophage activity after hemorrhagic shock and sepsis.

Hemorrhagic shock appears to predispose patients to subsequent sepsis. This study examined the effect of different resuscitation fluids on macrophage function following hemorrhagic shock. Male Sprague-Dawley rats were bled to a blood pressure of 50 mmHg for 60 min and then resuscitated with 6% hydroxyethyl starch (HES) or Lactated Ringers (LR). Phagocytic function was assessed by clearance of IV colloidal carbon (C). Carbon clearance was not statistically different between control (154.89), shock LR (169.16), and shock HES (144.60). Computerized image analysis of C distribution in sections of liver and spleen taken 4 h after C infusion exhibits a significant decrease in C distribution after resuscitation with HES compared to control and animals resuscitated with LR (Student's t test, p < .05). Male CBA/J mice were bled to a mean blood pressure of 50 mmHg for 60 min and then resuscitated with either LR (N = 18) or HES (N = 17). In separate experiments CBA/J mice had no shock, but were given LR or HES followed by cecal ligation and puncture and later excision (CLPE). A final group had shock with either LR or HES resuscitation and then CLPE as above. Splenocytes were harvested 48 h after shock for mixed lymphocyte culture (MLC). Animals undergoing shock with subsequent septic challenge (Shock/CLPE) showed significantly increased mortality 40 vs. 0% (chi square, p < .05) and immunosuppression on MLC 2,088(LR)/3,300 (HES) vs. 18,570 (LR)/17,705 (HES) compared to CLPE alone (Student's t test, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of isotonic crystalloid resuscitation on fluid compartments in hemorrhaged rats.

Redistribution of fluid after isotonic crystalloid resuscitation from hemorrhage may result not only in interstitial edema but also in cellular edema. We measured the extent to which shock and resuscitation altered fluid compartments in different organs. Nephrectomized, anesthetized rats were randomly divided into a Control group (n = 10) and a Hemorrhage plus Resuscitation group (H/R, n = 10). Rats were subjected to 60 min hemorrhagic hypotension (50 mmHg) followed by a 60 min resuscitation period with .9% NaCl infused as needed to maintain mean arterial pressure at 80% of baseline. A 2 h 51Cr-EDTA distribution space was used to estimate extracellular fluid volume (ECFV) and a 5 min 125I-albumin distribution space was used to measure plasma volume (PV). After euthanasia, total tissue water was measured by wet/dry weight analysis and interstitial fluid volume (ISFV) and cell water were calculated for selected organs. Resuscitation volume was two times the shed blood volume, but resulted in a PV equal to that of the Controls. There were no significant differences in whole animal ECFV or ISFV, although the mean values in the H/R group were greater than that of the Control group. The mean values for total tissue water for each tissue in the H/R group were larger than the respective means of the Control tissues but was significantly greater for only the heart (3639 +/- 56 microL/g vs. 3493 +/- 24 microL/g, mean +/- S.E., p < .05). In all H/R tissues, mean values for ISFV were also larger; this difference was significant for only the liver and small intestines (744 +/- 62 vs. 518 +/- 29 microL/g and 1117 +/- 155 vs. 706 +/- 58 microL/g, respectively). Heart cell water was significantly larger in H/R than Controls (2900 +/- 60 microL/g vs. 2738 +/- 27 microL/g). These data suggest that resuscitation of hemorrhage using isotonic crystalloid normalizes overall PV and ECFV but also causes interstitial expansion in selected gut tissues and cellular edema in the heart.

Animals↗

Xanthine oxidase inhibition after resuscitated hemorrhagic shock restores mesenteric blood flow without vasodilation.

To determine the contribution of xanthine oxidase-mediated reperfusion injury to the blood flow deficits seen in the intestinal microcirculation after resuscitated hemorrhagic shock, rats were prepared for intravital microscopic study then bled to 50% of baseline blood pressure for 60 min. Treatment animals received a 50 mg/kg bolus and a 25 mg/kg/h infusion of the xanthine oxidase inhibitor allopurinol after shock but before standard resuscitation with shed blood and an equal volume of Ringer's lactate. A similarly resuscitated group served as control. Blood flow and vessel diameters were measured in the neurovascularly intact terminal ileum using intravital microscopy and doppler velocimetry. Resuscitation restored cardiac output and blood pressure in both groups. Blood flow in first order arterioles 120 min postresuscitation was 41% of baseline in the standard resuscitation group and 77% of baseline in the allopurinol-treated group. A1 arteriolar diameter was not significantly different between the two groups, being 73 and 82% of baseline, respectively. These data suggest that xanthine oxidase-mediated ischemia-reperfusion injury contributes to blood flow deficits in the small intestinal microcirculation after resuscitated hemorrhagic shock and that the improvement in blood flow seen with allopurinol is not due to vasodilation within the microvasculature.

Allopurinol↗