Showing papers on "Resuscitation published in 2002"

Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality.

Abstract: Background Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP). One human trial has demonstrated improved survival when fluid resuscitation is restricted, whereas numerous laboratory studies have report

The importance of fracture pattern in guiding therapeutic decision-making in patients with hemorrhagic shock and pelvic ring disruptions.

Abstract: Background: Pelvic fractures may be associated with significant hemorrhage. Although this hemorrhage may emanate from the pelvic vasculature, it may also be secondary to abdominal visceral injury. The purpose of this study was to determine factors associated with pelvic and/or abdominal visceral bleeding in hypotensive patients with pelvic fractures to guide the appropriate therapeutic intervention sequence for these difficult-to-manage patients. Methods: Medical records of all hypotensive (systolic blood pressure ≤ 90 mm Hg) patients with pelvic fractures seen at a Level I trauma center from January 1995 to December 1999 were evaluated. Records were abstracted for age, base deficit, 24-hour blood requirement, hemoperitoneum (positive ultrasound, diagnostic peritoneal lavage, or computed tomographic scan), abdominal hemorrhage discovered at celiotomy, pelvic hemorrhage discovered at angiography, emergency department disposition, Injury Severity Score, and mortality. Pelvic fracture categories were derived by adapting the Young-Burgess pelvic fracture classification scheme. Lateral compression (LC) I and anteroposterior compression (APC) I fractures were characterized as stable fracture patterns (SFPs), and APC II, APC III, LC II, LC III, and vertical shear were characterized as unstable fracture patterns (UFPs). Results: Of 231 hypotensive patients, 38 patients died in the emergency department, leaving 193 surviving initial resuscitation. One hundred seven patients stabilized (group I) and were transferred to the intensive care unit. Eighty-six patients (group II) required ongoing resuscitation and underwent celiotomy and/or angiography in an attempt to manage their hemorrhage. Within group II, in the SFP population, abdominal hemorrhage was responsible for hypotension in 34 of 40 (85%), and 10 patients died (25%). In patients with UFP injury, hemorrhage was predominantly from a pelvic source, as shown by 27 positive angiograms in the 46 patients (59%). Twenty-four of 46 (52%) UFP patients died. In patients with a UFP, 14 had both angiography and celiotomy. Four patients underwent angiography before celiotomy and one of four (mortality, 25%) died. In contrast, 10 patients underwent celiotomy before angiography and 6 of 10 died (mortality, 60%). Conclusion: Patients with signs of ongoing shock with SFP pelvic injury and hemoperitoneum require celiotomy as the initial intervention, as the hemorrhagic focus is predominantly intraperitoneal. In patients with UFP, even in the presence of hemoperitoneum, consideration should be given to angiography before celiotomy.

Predictors of survival following in-hospital adult cardiopulmonary resuscitation

Abstract: Background: This study was undertaken to provide up-to-date survival data for Canadian adult in-patients following attempted resuscitation from cardiac or respiratory arrest. We hope that objective data might encourage more meaningful dialogue between physicians, patients and their families regarding resuscitation wishes. Methods: We reviewed all records of adult cardiopulmonary arrest that occurred between Jan. 1, 1997, and Jan. 31, 1999, at the 3 main teaching hospitals in Edmonton. We then abstracted data from the full inpatient medical records to describe patient characteristics, type of arrest and survival details. The family physicians of survivors were contacted to confirm the outcomes. We included only adults admitted to hospital but not to a critical care bed. Results: There were 247 arrests during the study period; 143 (57.9%) were witnessed, and 104 (42.1%) were unwitnessed). Of the patients whose arrests were witnessed, 48.3% (95% confidence interval [CI] 39.8%–56.8%) were able to be resuscitated, 22.4% (95% CI 15.8%–30.1%) survived to hospital discharge, and 18.9% (95% CI 12.8%–26.3%) were able to return home. Survival was highest after primary respiratory arrest and lowest after pulseless electrical activity or asystole. Of the patients with unwitnessed arrests, 21.2% (95% CI 13.8%–30.3%) were able to be resuscitated, but only 1 patient (1.0% [95% CI 0.0%–5.2%]) survived to hospital discharge and was able to return home. This patient survived an unwitnessed respiratory arrest. No patient who had an unwitnessed cardiac arrest survived to discharge. Most of the respiratory arrests were witnessed (93.1%), and most of the pulseless electrical activity or asystole arrests were unwitnessed (54.6%). We did not find age or sex to be independent predictors of survival. However, the risk of not returning home was higher among patients whose arrest occurred between 2301 and 0700 than among those whose arrest was between 0701 and 1500 (adjusted OR 3.2, 95% CI 1.0–10.1). Survival was significantly decreased after pulseless ventricular tachycardia or ventricular fibrillation arrest (adjusted OR 4.2, 95% CI 1.4–12.5) and even more so after pulseless electrical activity or asystole arrest (adjusted OR 21.0, 95% CI 6.2–71.7) than after respiratory arrest. Interpretation: Overall, survival following cardiopulmonary resuscitation in hospital does not appear to have changed markedly in 40 years. The type of arrest is highly predictive of survival, whereas age and sex are not.

Fluid resuscitation and hyperchloremic acidosis in experimental sepsis: Improved short-term survival and acid-base balance with Hextend compared with saline

Abstract: Objective To compare resuscitation with 0.9% saline with Hextend, a synthetic colloid in a balanced electrolyte solution, in terms of acid-base status and survival time in an experimental model of septic shock in the rat.Design Randomized, open-label, controlled experiment.Setting University researc

Out-of-Hospital Cardiac Arrest in Men and Women

Abstract: Background The incidence of sudden cardiac death is roughly 3 times greater in men than in women. However, in patients treated for out-of-hospital cardiac arrest, the relationships between sex and survival after adjustment for age and cardiac rhythm are unclear. Methods and Results In this retrospective cohort study, we examined 7069 men and 2582 women who were treated for out-of-hospital cardiac arrest in Seattle and suburban King County between 1990 and 1998. We compared successful prehospital resuscitation (hospital admission) and survival from event to discharge in men and women. Women had markedly reduced rates of ventricular fibrillation (VF), slightly older age, fewer witnessed arrests, and fewer arrests in public locations than men. Although their unadjusted resuscitation rate was lower (29% versus 32%, P<0.0001), women had a greater likelihood of resuscitation than men after adjustment for VF (odds ratio [OR] 1.13; 95% confidence interval [CI], 1.03 to 1.25) and after adjustment for VF plus addit...

Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1

Abstract: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit HIF-1beta. In this study we analyzed HIF-1alpha expression in the rat cerebral cortex after transient global ischemia induced by cardiac arrest and resuscitation. Our results showed that HIF-1alpha accumulates as early as 1 hr of recovery and persists for at least 7 d. In addition, the expression of HIF-1 target genes, erythropoietin and Glut-1, were induced at 12 hr to 7d of recovery. A logical explanation for HIF-1alpha accumulation might be that the brain remained hypoxic for prolonged periods after resuscitation. By using the hypoxic marker 2-(2-nitroimidazole-1[H]-y1)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5), we showed that the brain is hypoxic during the first hours of recovery from cardiac arrest, but the tissue is no longer hypoxic at 2 d. Thus, the initial ischemic episode must have activated other nonhypoxic mechanisms that maintain prolonged HIF-1alpha accumulation. One such mechanism might be initiated by insulin-like growth factor-1 (IGF-1). Our results showed that IGF-1 expression was upregulated after cardiac arrest and resuscitation. In addition, we showed that IGF-1 was able to induce HIF-1alpha in pheochromocytoma cells and cultured neurons as well as in the brain of rats that received intracerebroventricular and systemic IGF-1 infusion. Moreover, infusion of a selective IGF-1 receptor antagonist abrogates HIF-1alpha accumulation after cardiac arrest and resuscitation. Our study suggest that activation of HIF-1 might be part of the mechanism by which IGF-1 promotes cell survival after cerebral ischemia.

Secondary abdominal compartment syndrome is an elusive early complication of traumatic shock resuscitation.

Abstract: Background The term secondary abdominal compartment syndrome (ACS) has been applied to describe trauma patients who develop ACS but do not have abdominal injuries. The purpose of this study was to describe major trauma victims who developed secondary ACS during standardized shock resuscitation. Methods Our prospective database for standardized shock resuscitation was reviewed to obtain before and after abdominal decompression shock related data for secondary ACS patients. Focused chart review was done to confirm time-related outcomes. Results Over the 30 months period ending May 2001, 11 (9%) of 128 standardized shock resuscitation patients developed secondary ACS. All presented in severe shock (systolic blood pressure 85 ± 5 mm Hg, base deficit 8.6 ± 1.6 mEq/L), with severe injuries (injury severity score 28 ± 3) and required aggressive shock resuscitation (26 ± 2 units of blood, 38 ± 3 L crystalloid within 24 hours). All cases of secondary ACS were recognized and decompressed within 24 hours of hospital admission. After decompression, the bladder pressure and the systemic vascular resistance decreased, while the mean arterial pressure, cardiac index, and static lung compliance increased. The mortality rate was 54%. Those who died failed to respond to decompression with increased cardiac index and did not maintain decreased bladder pressure. Conclusions: Secondary ACS is an early but, if appropriately monitored, recognizable complication in patients with major nonabdominal trauma who require aggressive resuscitation.

Tissue plasminogen activator in cardiac arrest with pulseless electrical activity

Abstract: Background Coronary thrombosis and pulmonary thromboembolism are common causes of cardiac arrest. We assessed whether the administration of tissue plasminogen activator (t-PA) during cardiopulmonary resuscitation would benefit patients with cardiac arrest and pulseless electrical activity of unknown or presumed cardiovascular cause. Methods Patients who were older than 16 years of age and who had more than one minute of pulseless electrical activity that was unresponsive to initial therapy outside the hospital or in the emergency department were eligible. Patients were randomly assigned to receive 100 mg of t-PA or placebo intravenously over a 15-minute period in a double-blind fashion. Standard resuscitation was then continued for at least 15 minutes. The primary outcome was survival to hospital discharge. Results During the study period, 1583 patients with cardiac arrest were treated and 233 patients were enrolled (117 in the t-PA group and 116 in the placebo group). The characteristics of the patients in the two groups were similar. One patient in the t-PA group survived to hospital discharge, as compared with none in the placebo group (absolute difference between groups, 0.9; 95 percent confidence interval, i2.6 to 4.8; P=0.99). The proportion of patients with return of spontaneous circulation was 21.4 percent in the t-PA group and 23.3 percent in the placebo group (absolute difference between groups, i1.9; 95 percent confidence interval, i12.6 to 8.8; P=0.85). Conclusions We found no evidence of a beneficial effect of fibrinolysis in patients with cardiac arrest and pulseless electrical activity of unknown or presumed cardiovascular cause. Our study had limited statistical power, and it remains unknown whether there is a small treatment effect or whether selected subgroups may benefit. (N Engl J Med 2002;346:1522-8.)

Effect on outcome of early intensive management of geriatric trauma patients.

Abstract: Background: Despite significant injuries elderly patients (aged 70 years or more) often do not exhibit any of the standard physiological criteria for trauma team activation (TTA), i.e. hypotension, tachycardia or unresponsiveness to pain. As a result of these findings the authors' TTA criteria were modified to include age 70 years or more, and a protocol of early aggressive monitoring and resuscitation was introduced. The aim of the present study was to assess the effect of the new policy on outcome. Methods: This trauma registry study included patients aged 70 years or more with an Injury Severity Score (ISS) greater than 15 who were admitted over a period of 8 years and 8 months. The patients were divided into two groups: group 1 included patients admitted before age 70 years and above became a TTA criterion and group 2 included patients admitted during the period when age 70 years or more was a TTA criterion and the new management protocol was in place. The two groups were compared with regard to survival, functional status on discharge and hospital charges. Results: There were 336 trauma patients who met the criteria, 260 in group 1 and 76 in group 2. The two groups were similar with respect to mechanism of injury, age, gender, ISS and body area Abbreviated Injury Score. The mortality rate in group 1 was 53·8 per cent and that in group 2 was 34·2 per cent (P = 0·003) (relative risk (RR) 1·57 (95 per cent confidence interval 1·13 to 2·19)). The incidence of permanent disability in the two groups was 16·7 and 12·0 per cent respectively (P = 0·49) (RR 1·39 (0·59 to 3·25)). In subgroups of patients with an ISS of more than 20 the mortality rate was 68·4 and 46·9 per cent in groups 1 and 2 respectively (P = 0·01) (RR 1·46 (1·06 to 2·00)); 12 of 49 survivors in group 1 and two of 26 in group 2 suffered permanent disability (P = 0·12) (RR 3·18 (0·77 to 13·20)). Conclusion: Activation of the trauma team and early intensive monitoring, evaluation and resuscitation of geriatric trauma patients improves survival. © 2002 British Journal of Surgery Society Ltd

Outcome after Cardiopulmonary Resuscitation in Patients with Pulmonary Arterial Hypertension

Abstract: Patients with pulmonary arterial hypertension (PAH) often die from right heart failure or sudden cardiac death. Cardiopulmonary resuscitation (CPR) may be instituted in these patients but there are no data in the medical literature about the outcome of CPR in this group of patients. We conducted a retrospective multicenter international study on the frequency and results of CPR in patients with PAH. A total of 3,130 patients with PAH were treated between 1997 and 2000 in 17 referral centers in Europe and in the United States. During this period, 513 patients had circulatory arrest and CPR was attempted in 132 (26%) of these patients. Although 96% of the CPR attempts took place in hospitalized patients (74% in intensive care units or equally equipped facilities) and although there was only minimal delay between collapse and initiation of CPR, resuscitation efforts were primarily unsuccessful in 104 patients (79%). Only eight patients (6%) survived for more than 90 d; these patients had no residual neurologic deficit. Hemodynamics obtained within 3 mo before CPR did not show any significant differences between the survivors and nonsurvivors. Except for one patient, all long-term survivors had identifiable causes of circulatory arrest that were rapidly reversible. Our data indicate that CPR for circulatory arrest in patients with PAH is rarely successful unless the cause of the cardiopulmonary decompensation can be corrected.

Cerebral resuscitation potentials for cardiac arrest.

Abstract: Permanent brain damage after cardiac arrest and resuscitation is determined by many factors, predominantly arrest (no-flow) time, cardiopulmonary resuscitation (low-flow) time, and temperature. Research since around 1970 into cardiopulmonary-cerebral resuscitation has attempted to mitigate the postischemic-anoxic encephalopathy. These efforts' results have recently shown outcome benefits as documented in clinically relevant outcome models in dogs and in clinical trials. Pharmacologic strategies have so far yielded relatively disappointing results. In a recent exploration of 14 drugs in dogs, only the antioxidant tempol administered at the start of prolonged cardiac arrest improved functional outcome in dogs. Cerebral blood flow promotion by hypertensive reperfusion and hemodilution has resulted in improved outcome in dogs, and brief hypertension after restoration of spontaneous circulation is associated with improved outcome in patients. Postarrest hypercoagulability of blood seems to yield to therapeutic thrombolysis, which is associated with improved cerebral outcome in animals and patients. In a clinically relevant dog outcome model, mild postarrest cerebral hypothermia (34 degrees C), initiated with reperfusion and continued for 12 hrs, combined with cerebral blood-flow promotion increased from 5 to >10 mins the previously longest normothermic no-flow time that could be reversed to complete cerebral recovery. Mild hypothermia by surface cooling after prolonged cardiac arrest in patients has been found effective in recent clinical studies in Australia and Europe. Preliminary data on the recent randomized study in Europe have been reported. For presently unresuscitable cardiac arrests, research since the 1980s in dog outcome models of prolonged exsanguination cardiac arrest has culminated in brain and organism preservation during cardiac arrest (no-flow) durations of up to 90 mins, perhaps 120 mins, at a tympanic temperature of 10 degrees C and complete recovery of function and normal histology. This "suspended animation for delayed resuscitation" strategy includes use of an aortic flush of cold saline (or preservation solution) within the first 5 mins of no flow. This strategy should also be explored for the larger number of patients with unresuscitable out-of-hospital cardiac arrests. Suspended animation for prolonged preservation of viability could buy time for transport and repair during hypothermic no flow followed by resuscitation, or it could serve as a bridge to prolonged cardiopulmonary bypass.

Resuscitation from hemorrhagic shock with ringer's ethyl pyruvate solution improves survival and ameliorates intestinal mucosal hyperpermeability in rats

Abstract: We previously showed that pretreatment with a solution of ethyl pyruvate in a calcium-containing balanced salt solution, Ringer's ethyl pyruvate solution (REPS), ameliorates gut mucosal damage in rats subjected to mesenteric ischemia/reperfusion. Herein, we sought to test the hypothesis that REPS would be beneficial as a post-treatment (i.e., resuscitation fluid) for hemorrhagic shock. Anesthetized Sprague-Dawley rats were bled to a mean arterial pressure (MAP) of 40 mmHg until 40% of shed blood was returned. The animals then were resuscitated over 60 min with the remaining shed blood plus twice the shed blood volume as either Ringer's lactate solution (RLS) or REPS. In Experiment 1, RLS or REPS was then infused for 3 h more (or until death) at 3 mL/kg/h. Read-outs were post-resuscitation ileal mucosal permeability to fluorescein-labeled Dextran with an average molecular mass of 4000 Da (FD4) and survival. Permeability, determined just before death (MAP < 40 mmHg) or afte r4ho fresuscitation, was assessed using an ex vivo everted gut sac technique and is expressed as a clearance (nL/cm/min). In Experiment 2, the read-outs were ileal FD4 permeability measured at 60 min after starting resuscitation and gut and liver malondialdehyde (MDA) formation. FD4 clearance data were logarithmically transformed prior to performing statistical analyses. In Experiment 1, 4/8 (50%) of RLS-treated rats survived 4 h after resuscitation whereas 7/7 (100%) of REPS-treated rats survived (P < 0.05). Ileal FD4 clearances were 105 ± 30*, 85 ± 34*, and 38 ± 7 for all rats treated with RLS, surviving rats treated with RLS, and rats treated with REPS, respectively (the asterisk indicates P < 0.05 vs. REPS). In Experiment 2, ileal FD4 clearances were 71 ± 13* and 34 ± 8 for rats treated with RLS and REPS (n = 5 each), respectively. Post-resuscitation levels of MDA in the ileum and liver were significantly lower in rats treated with REPS as compared with RLS. Resuscitation with REPS, a stable and nontoxic antioxidant solution, improves survival and ameliorates ileal mucosal permeability in a rat model of severe hemorrhagic shock. KEYWORDS—Epithelium, intestinal, antioxidant, malondialdehyde, permeability, hydrogen peroxide

How well does the Parkland formula estimate actual fluid resuscitation volumes

Abstract: We had anecdotally observed that fluid resuscitation volumes often exceed those estimated by the Parkland Formula in adults with isolated cutaneous burns. The purpose of this study was to compare estimated and actual fluid resuscitation volumes using the Parkland Formula. We performed a retrospective study of fluid resuscitation in patients with burns > or = 15% TBSA. Patients with inhalation injury, high voltage electrical injury, delayed resuscitation, or associated trauma were excluded. We studied 31 patients (mean age 51 +/- 20 years, mean TBSA burn 27 +/- 10%). The 24 hour resuscitation volume of 13 354 +/- 7386 ml (6.7 +/- 2.8 ml/kg/%TBSA) was significantly greater than predicted (P = 0.001) and exceeded estimated volume in 84% of the patients. The mean urine output in the first 24 hrs was 1.2 +/- 0.6 ml/kg/hr. After the first 8 hours of resuscitation, the infusion rate decreased by 34% in 16 patients (DCR group), while in 15 patients the rate increased by 47% (INCR group). Both the DCR and INCR groups received significantly more fluid than predicted, (5.6 +/- 2.1 ml/kg/%TBSA and 7.7 +/- 3.1 ml/kg/%TBSA respectively). The INCR patients had significantly larger full thickness burns (14 +/- 11% vs 3 +/- 6%, P < 0.001). Our findings reveal that despite its effectiveness, the Parkland Formula underestimated the volume requirements in most adults with isolated cutaneous burns, and especially in those with large full thickness burns.

Hypothermic Reperfusion After Cardiac Arrest Augments Brain-Derived Neurotrophic Factor Activation

Abstract: Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37°C) or cooled to mild hypothermia (33°C, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest.

Hypertonic Saline Resuscitation of Hemorrhagic Shock Diminishes Neutrophil Rolling and Adherence to Endothelium and Reduces In Vivo Vascular Leakage

Abstract: Over 30 years ago, the Vietnam War established the current standard use of isotonic crystalloid fluids (normal saline [NS] and Ringer’s lactate [RL]) for the resuscitation of hemorrhagic shock. Subsequent studies have demonstrated that crystalloids represent an effective and inexpensive means to restore intravascular volume and additionally offer a survival advantage over colloids in the resuscitation of traumatic hemorrhagic shock. 1 More recently, “small volume resuscitation”2 with 4 mL of 7.5% NaCl per kilogram of body weight of hypertonic saline (HTS) has been proposed in the treatment of hemorrhagic shock. Whereas isotonic fluid administration requires large volumes, hypertonic resuscitation offers the advantages of ease of transport, speed of administration, and almost instantaneous hemodynamic effect. The intravascular administration of 7.5% NaCl rapidly creates a potent transcapillary osmotic gradient causing intravascular movement of water from the interstitium, endothelial cells (ECs), and red blood cells, a process that could reduce third-space fluid sequestration in the lungs of patients with traumatic pulmonary contusions or in the brain following head trauma. 3 Early animal studies showed that HTS resuscitation rapidly restored mean arterial pressure (MAP), peripheral tissue perfusion, cardiac contractility, and oxygen consumption, mainly through vasodilatation of precapillary resistance vessels and increases in cardiac preload. 4–6 Although large multicentric randomized human clinical trials subsequently confirmed that HTS resuscitation was safe and efficacious, they failed to demonstrate a clear survival advantage over standard isotonic resuscitation. 4,7 Nonetheless, one multicentric randomized control trial has demonstrated fewer postresuscitation complications, such as ARDS, renal failure, and coagulopathies, with the use of HTS. 4 Many of the complications following the resuscitation of hemorrhagic shock may be related to alterations in host immunity. In particular, the polymorphonuclear neutrophil (PMN), one of the principal host immune effector cells, has been implicated in the development of organ dysfunction and death following sepsis, burns, and multiple trauma as well as hemorrhagic shock resuscitation. 8–10 Although the PMN is essential in protecting the host from traumatic and infectious insults, it may also turn its potent defenses inappropriately against the host, activated by and contributing to the severity of injury. The sequential events in the passage of PMNs from the vasculature to their sites of action have been well characterized. First marginating to the periphery of the vessel, the PMN rolls on the vessel wall, interacting with ECs through surface selectins (L, E, and P). 11 These weak interactions allow PMN β2-integrins (CD18/CD11) to strongly interact with endothelial receptors of the Ig superfamily (ICAM-1, ICAM-2), 12 resulting in firm adhesion of the two cell types and permitting subsequent PMN diapedesis between ECs to reach the injured site. 13 The inappropriate upregulation of these PMN–EC interactions in the ischemia/reperfusion injury of hemorrhagic shock resuscitation is believed to be an important step in the host’s progression to systemic inflammation and subsequent remote organ injury. There are data suggesting that activated PMNs are then sequestered in end organs, where they unleash a cytotoxic arsenal of proteases and oxygen radicals, causing injury to endothelium and resulting in vascular leakage, tissue edema, and eventually organ damage. 8,10,14 Much evidence now exists demonstrating that HTS resuscitation of hemorrhagic shock alters PMN activity. When human PMNs are incubated in hypertonic media, they display decreased cytotoxicity, cellular activation, superoxide production, and elastase release. 15–19 In vivo studies suggest that both neutrophil and endothelial adhesion molecule expression is reduced in HTS-resuscitated animals as compared to those receiving RL. 15,20–22 These alterations in adhesion molecules suggest that HTS may impart functional changes in PMNs and ECs. More importantly, animal models of hemorrhagic shock resuscitated with HTS have shown reductions in lung and liver injury, diminished bronchioalveolar lavage PMNs, and diminished pulmonary myeloperoxidase (MPO - total PMN content) as well as decreases in mortality. 15,21,23 Models of hemorrhagic shock resuscitation studied with intravital microscopy suggest that the beneficial effects of HTS may be due to altered EC–PMN interactions. 24–26 However, the consequences of such altered EC–PMN interactions following HTS resuscitation of hemorrhagic shock remain elusive, and the links to altered adhesion molecule expression and to subsequent tissue edema are unclear. We thus hypothesized that through diminished endothelial ICAM-1 expression, HTS resuscitation of hemorrhagic shock lessens venular EC–PMN interactions, leading to decreased in vivo vascular leakage in remote organs. We tested this hypothesis in a murine model of resuscitated hemorrhagic shock using intravital microscopy of cremaster muscle.

IL-1beta and IL-6 act synergistically with TNF-alpha to alter cardiac contractile function after burn trauma.

Abstract: Although numerous studies have provided evidence that the inflammatory cytokines TNF-alpha and IL-1beta have significant negative inotropic effects, the role of the interleukins in burn-mediated cardiac dysfunction has not been defined. Furthermore, most studies examining the cardiotoxic effects of inflammatory cytokines have ignored the complex inflammatory milieu that occurs in the intact subject with trauma, sepsis, or ischemic heart disease. Therefore, this study examined the time course of IL-1beta and IL-6 secretion by cardiomyocytes after burn trauma, and additional studies examined the effects of these cytokines alone or in combination with TNF-alpha on cardiac contractile performance (Langendorff). Sprague-Dawley rats were given a full thickness burn injury over 40% of the total body surface area; fluid resuscitation was lactated Ringers solution, 4 mL/kg per burn percentage of burn area. Sham burn animals received identical anesthesia and handling, but no burn injury. Rats were sacrificed at several different times postburn, and isolated hearts (n = 4-5 rats/group/time period) were perfused with collagenase-containing buffer to prepare cardiomyocytes or were perfused in vitro to examine cardiac contractile function (n = 5-6 rats/group/time period). Additional naive control rats (n = 10) were included to prepare cardiomyocytes that, in turn, were challenged with different concentrations of either IL-1beta, IL-6, or TNF-alpha alone or in combination for several time periods (CO2 incubator at 37 degrees C for 1-3 h). Finally, inflammatory cytokines alone or in combination were added to the perfusate of hearts isolated from additional control rats (n = 6-7/group) to assess the cardiac contraction and relaxation effects of cytokine challenge. Despite aggressive fluid resuscitation, burn trauma produced a time-related increase in cardiomyocyte secretion of IL-1beta, IL-6, and TNF-alpha. Exposure of naive cardiomyocytes prepared from control rats to each cytokine alone or combined cytokine challenge produced a time-dependent and concentration-dependent decrease in cell viability and an increase in supernatant creatine kinase levels. Either IL-1beta or TNF-alpha produced greater cardiac defects than IL-6 when added separately to Langendorff-perfused hearts; dysfunction was maximal with combined cytokine challenge (IL-1beta plus TNF-alpha plus IL-6). The data confirm that burn trauma upregulates inflammatory cytokine secretion by cardiomyocytes and suggest that these inflammatory cytokines act in concert to produce burn-mediated cardiac contractile dysfunction.

Small-volume resuscitation: from experimental evidence to clinical routine. Advantages and disadvantages of hypertonic solutions.

Abstract: Background: The concept of small-volume resuscitatioin (SVR) using hypertonic solutions encompasses the rapid infusion of a small dose (4 ml per kg body weight, i.e. approximately 250 ml in an adult patient) of 7.2–7.5% NaCl/colloid solution. Originally, SVR was aimed for initial therapy of severe hypovolemia and shock associated with trauma. Methods: The present review focusses on the findings concerning the working mechanisms responsible for the rapid onset of the circulatory effect, the impact of the colloid component on microcirculatory resuscitation, and describes the indications for its application in the preclinical scenario as well as perioperatively and in intensive care medicine. Results: With respect to the actual data base of clinical trials SVR seems to be superior to conventional volume therapy with regard to faster normalization of microvascular perfusion during shock phases and early resumption of organ function. Particularly patients with head trauma in association with systemic hypotension appear to benefit. Besides, potential indications for this concept include cardiac and cardiovascular surgery (attenuation of reperfusion injury during declamping phase) and burn injury. The review also describes disadvantaages and potential adverse effects of SVR: Conclusion: Small-volume resuscitation by means of hypertonic NaCl/colloid solutions stands for one of the most innovative concepts for primary resuscitation from trauma and shock established in the past decade. Today the spectrum of potential indications envolves not only prehospital trauma care, but also perioperative and intensive care therapy.

Managing the unique size-related issues of pediatric resuscitation: reducing cognitive load with resuscitation aids.

Abstract: A resuscitation is a complicated event that requires for its optimal outcome the effective completion of a distinct series of actions, some simple, some complex, most occurring simultaneously or in close proximity. In children, these actions are determined not only by the clinical situation, but also by a series of age and size factors particular to each child. Different tasks require different levels of cognitive load, or mental effort. Cognitive load describes the mental burden experienced by the decision maker and will be higher when the task is less familiar or more demanding. In the setting of resuscitation, it refers to the cumulative demands of patient assessment, the ongoing decisions for each of the various steps, and decisions around procedural intervention (e.g., intubation). In children, the level of task complexity and, hence, cognitive load is increased by the unique component of variability of pediatric age and size, introducing logistical factors, many of which involve computations. The purpose of this paper is to examine the effects of age/size-related variables on the pediatric resuscitative process and to explore how these effects can be mitigated using resuscitation aids. The concept of cognitive load and its relation to performance in resuscitation is introduced and is used to demonstrate the effect of the various aids in the pediatric resuscitative process.

Pelvic radiography in blunt trauma resuscitation: a diminishing role.

Abstract: Background: An anteroposterior pelvic radiograph (PXR) continues to be recommended by Advanced Trauma Life Support protocol as an early diagnostic adjunct in the resuscitation of blunt trauma patients. At the same time, computed tomographic (CT) scanning has become a practice standard for diagnosis of most abdominal and pelvic injury. The objective of this study was to determine the necessity of obtaining an early PXR in stable trauma patients who will undergo CT scanning during the initial resuscitation. Methods: A retrospective review of all blunt trauma patients undergoing immediate abdomen and pelvic CT scanning was performed from July 2000 until June 2001 at an urban Level I trauma center. These patients were divided into two groups depending on whether they also received a PXR (group I) or not (group II). At the time of the study, there was no formal protocol to determine which patients underwent pelvic radiography. Radiology reports of all PXRs and CT scans were reviewed. Patient demographics and Injury Severity Scores (ISSs) were abstracted from our trauma registry. The data were analyzed using Student's t test. Results: A total of 686 patients with blunt trauma underwent CT scanning of the abdomen and pelvis. Group I consisted of 311 (45%) patients with an average ISS of 12.3 ± 0.7. In group 1, 56 (10%) patients were found to have at least one pelvic fracture on CT scan, 38 of which were also identified on the PXR. Defining CT scanning as the definitive test, the sensitivity and specificity of the PXR in group I was 68% and 98%, respectively. The false-negative rate for pelvic radiography was 32%. In all patients with a positive PXR, the majority (55%) had either additional fractures or an increase in the Young and Burgess grade of fracture diagnosed on CT scan. Group II consisted of 375 patients, with 16 fractures noted in 13 (3%) patients, none of which required treatment. The mean ISS of group II was 8.0 ± 0.5. Conclusion: The PXR has limited sensitivity for detecting pelvic fractures compared with CT scanning. Selected hemodynamically stable patients who undergo CT scanning during their immediate resuscitation do not need a routine PXR. The PXR may continue to be beneficial in unstable patients, those with positive physical findings, or those who cannot undergo CT scanning because of other clinical priorities.

Regulation of Toll-Like Receptor 4 Expression in the Lung Following Hemorrhagic Shock and Lipopolysaccharide

Abstract: The Toll-like receptor 4 (TLR4) has recently been shown to function as the major upstream sensor for LPS. In this study, a rodent model of lung injury following resuscitated hemorrhagic shock was used to examine the regulation of TLR4 gene and protein expression in vivo and in vitro. Intratracheal LPS alone induced a rapid reduction in whole lung TLR4 mRNA, an effect which is also observed in recovered alveolar macrophages. This effect appeared to be due to a lowering of TLR4 mRNA stability by ∼69%. By contrast, while shock/resuscitation alone had no effect on TLR4 mRNA levels, it markedly altered the response to LPS. Specifically, antecedent shock prevented the LPS-induced reduction in TLR4 mRNA levels. This reversal was explained by the ability of prior resuscitated shock both to prevent the destabilization of TLR4 mRNA by LPS and also to augment LPS-stimulated TLR4 gene transcription compared with LPS alone. Oxidant stress related to shock/resuscitation appeared to contribute to the regulation of TLR4 mRNA, because supplementation of the resuscitation fluid with the antioxidant N-acetylcysteine reversed the ability of shock/resuscitation to preserve TLR4 mRNA levels following LPS. TLR4 protein levels in whole lung mirrored the changes seen for TLR4 mRNA. Considered in aggregate, these data suggest that levels of tlr4 expression are controlled both transcriptionally as well as posttranscriptionally through altered mRNA stability and that antecedent shock/resuscitation, a form of global ischemia/reperfusion, might influence regulation of this gene.

Derivation of a termination-of-resuscitation guideline for emergency medical technicians using automated external defibrillators

Abstract: Objectives To determine the association between characteristics of cardiac arrest and survival to hospital discharge following failed resuscitation by defibrillation-trained emergency medical technicians (EMT-Ds), and to propose an out-of-hospital termination-of-resuscitation (TOR) guideline for EMT-Ds. Methods A 22-month retrospective review of 700 out-of-hospital primary cardiac arrest patients in a large emergency medical services (EMS) system who received exclusively EMT-D care. Results Seven hundred primary cardiac arrest patients were identified. Follow-up was obtained in 662 cases (94.6%). Of these, 36 (5.4%) achieved a return of spontaneous circulation (ROSC) prior to transport. Among the 626 patients who failed to achieve ROSC at any time, two (0.3%) survived to discharge. Multivariate analysis showed that ROSC at any time had the strongest association with survival [odds ratio (OR) 45.5; 95% confidence interval (95% CI) = 8.5 to 243.7]. A shock prior to transport (OR 6.9; 95% CI = 1.2 to 40.3) and cardiac arrest witnessed by EMS personnel (OR 4.4; 95% CI = 1.0 to 18.5) were also independently associated with survival. These variables were incorporated into a TOR guideline. The guideline was 100% sensitive (95% CI = 99.1 to 100) in identifying survivors and had 100% negative predictive value (95% CI = 75.3 to 100) for identifying nonsurvivors of out-of-hospital cardiac arrest in the study population. Conclusions In this EMS system, cardiac arrest patients may be considered for out-of-hospital TOR following EMT-D resuscitation attempts when there has been no ROSC, no shock has been given, and the arrest was not witnessed by EMS personnel. These guidelines require prospective validation.

The time course of cardiac NF-kappaB activation and TNF-alpha secretion by cardiac myocytes after burn injury: contribution to burn-related cardiac contractile dysfunction.

Abstract: Previous studies have suggested that cardiac synthesis of TNF-alpha contributes to myocardial dysfunction in several models of trauma, sepsis and ischemia. Therefore, it is likely that myocyte secretion of TNF-alpha occurs early after major burn trauma, contributing to progressive cardiac contractile dysfunction that is characteristic of thermal injury. This study examined the time course of nuclear translocation of the transcription factor NF-kappaB, the time course of TNF-alpha secretion by cardiomyocytes after burn trauma, and the development of cardiac contractile defects. Rats were given burn injury over 40% TBSA (sham burns included for controls), and fluid resuscitation included lactated Ringer's solution, 4 mL/kg/%burn. Subsets of rats were sacrificed at several times postburn (1, 2, 4, 8, 12, 18 and 24 h), hearts were harvested to prepare cardiomyocytes (N = 4 rats/group/time period), to prepare nuclear fractions to measure burn-induced NF-kappaB activation (N = 3-4 rats/group/time period), or to examine the time course of postburn cardiac contractile dysfunction (N = 6-7 rats/group/time period). Despite aggressive fluid resuscitation, burn trauma activated NF-kappaB 4 h postburn, and this activation persisted over the 24 h study period. In addition, burn trauma produced a time-related increase in TNF-alpha secretion by cardiac myocytes with cytokine secretion evident 1 h postburn. Cardiac dysfunction occurred 8 h postburn and persisted over the 24 h study period. Administration of a strategy designed to inhibit NF-kappaB activation (N-acetyl-leucinyl-leucinyl-norleucinal, ALLN, 50 mg/kg, in additional groups of burn rats) inhibited TNF-alpha secretion by cardiac myocytes and improved myocardial function. This study confirms that burn trauma activates myocardial NF-kappaB and promotes cardiomyocyte secretion of TNF-alpha. This inflammatory cascade preceded the appearance of cardiac dysfunction, suggesting that cardiac myocyte derived TNF-alpha contributes, in part, to postburn cardiac contractile deficits.

Hepatic angiography in patients undergoing damage control laparotomy

Abstract: Objective: Patients undergoing damage control (DC) laparotomy require intensive and aggressive resuscitation, and may require additional maneuvers to control parenchymal bleeding. Those patients suffering significant liver injury are at high risk for arterial bleeding deep within the liver, and many require hepatic angiography in addition to hepatic packing. We reviewed our experience with hepatic angiography, and sought to determine its safety in the DC population of penetrating and blunt trauma patients. Methods: A 3-year (June 1997-May 2000) retrospective review generated 37 DC patients. Patients sustaining hepatic trauma constituted the study group. Patients undergoing angiography in addition to DC laparotomy were compared with the group of patients not undergoing angiography. Data regarding mechanism of injury, patient demographics, extent of hepatic injury, and presence of associated injuries were collected. Physiologic parameters including vital signs at admission, lowest pH and base excess in the operating room, and lactate levels in the intensive care unit, as well as volumes of fluid resuscitation throughout all phases of DC were examined. Complications including death, intra-abdominal processes, acute respiratory distress syndrome and/or multiple organ dysfunction syndrome, and acute renal failure were reviewed. Results: Nineteen patients (51%) had hepatic trauma and underwent perihepatic packing as a part of DC laparotomy. Eleven had sustained penetrating injury and 8 had blunt injury. There was I American Association for the Surgery of Trauma grade I, 5 grade II, 3 grade III, and 10 grade IV injuries. Nine patients in the study population underwent angiography, and eight of these were hepatic artery angiograms. One hepatic angiogram was obtained before operation and seven were obtained in the immediate postoperative period. Six underwent embolization of bleeding hepatic vessels, for a therapeutic liver angiography rate of 75%. There was no statistical difference in physiologic parameters or fluid requirements between the patients who underwent angiography and those who did not. There were no mishaps or complications from angiography or while in the angiography suite. Conclusion: Hepatic angiography is a safe adjunct to the principles of damage control. It has a high therapeutic ratio, with no significant untoward effect in this small study population.

Should parents be present during emergency department procedures on children, and who should make that decision? A survey of emergency physician and nurse attitudes.

Abstract: Objective: To survey physician and nurse attitudes regarding parental presence during painful procedures on children performed in the emergency department (ED) and who should make that decision. Methods: The design was an anonymous written survey consisting of six clinical scenarios distributed to all staff and resident physicians and nurses in ten EDs at institutions in the United States routinely caring for children. Participants were asked whether parents should remain with children undergoing intravenous (IV) placement, laceration repair, lumbar puncture, conscious sedation, major resuscitation, and major resuscitation with death. They also were asked who should make the decision. Results: The percentage of physicians who responded that parents should be present was 91.3% for peripheral IV start, 93.3% for laceration repair, 65.7% for lumbar puncture, 83.1% for conscious sedation, 31.9% for major resuscitation, and 35.6% for major resuscitation where death was likely. The percentage of nurses who responded that parents should be present was 86.8% for peripheral IV start, 89.6% for laceration repair, 55.0% for lumbar puncture, 74.9% for conscious sedation, 41.4% for major resuscitation, and 54.3% for major resuscitation where death was likely. In 64.8% of the completed surveys, the physicians indicated that they alone or in conjunction with a parent should make the decision. In 61.5% of the completed surveys, the nurses indicated that they should be involved in the decision. Conclusions: A majority of emergency physicians and nurses indicated parents should be present for some invasive pediatric procedures. However, as the invasiveness of the pediatric procedures increased, fewer physicians and nurses believed that parents should be present.

Hypertonic saline improves intestinal mucosa barrier function and lung injury after trauma-hemorrhagic shock.

Abstract: Our objective was to test the hypotheses that small volume hypertonic saline (HTS) resuscitation protects against trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury better than standard volume resuscitation with Ringer's lactate (RL), and that the degree of lung injury correlates with the degree of gut injury after therapy. Male Sprague-Dawley rats were subjected to laparotomy (trauma) and 90 min of T/HS or sham shock (T/SS), and were then resuscitated with RL or 7.5% NaCl solution at an equivalent sodium load. Intestinal and lung injury was assessed at 3 and 24 h after resuscitation. Lung permeability, pulmonary myeloperoxidase (MPO) levels, and the bronchoalveolar lavage fluid (BALF) protein to plasma protein ratio were increased after T/HS, but were significantly lower in HTS-resuscitated than RL-treated rats. The incidence of bacterial translocation (BT) was not different between the groups, but the magnitude of BT after T/HS was less after HTS than RL resuscitation. Barrier function of intestinal segments was impaired only in the T/HS rats resuscitated with RL and histological analysis demonstrated fewer injured villi in the T/HS rats resuscitated with HTS than RL. Linear regression analysis revealed direct correlations between the percent of injured villi, increased lung permeability, and pulmonary neutrophil sequestration. Resuscitation with HTS ameliorated T/HS-induced gut and lung injury seen with RL resuscitation. These results, together with the direct correlation found between gut and lung injury, suggest that lung injury after T/HS may be mediated by gut injury.