Hypothermia is associated with improved outcomes in a porcine model of hemorrhagic shock.

BACKGROUND: : Hypothermia after trauma is, in current medical practice, both avoided and aggressively treated. However, the effects of environmental hypothermia during early resuscitation after hemorrhagic shock have been only poorly characterized. METHODS: : The objective of our study was to compare normothermia versus mild and severe levels of hypothermia in a porcine model of hemorrhagic shock. In a prospective survival study, we anesthetized 19 juvenile male pigs (Yorkshire-Landrace, 15-25 kg) and caused them to hemorrhage until their systolic blood pressure was 45 mm Hg to 55 mm Hg for a duration of 45 minutes. Then, we randomized them into three groups (all of which underwent an 8-hour limited resuscitation period) as follows: normothermic (39 degrees C), mildly hypothermic (36 degrees C), and severely hypothermic (33 degrees C). We used ice packs to achieve surface cooling that mimicked environmental hypothermia. After 8 hours, we rewarmed the pigs and fully resuscitated them for 16 hours. We extubated the survivors and observed them for an additional 24 hours, before killing them. RESULTS: : Surface cooling resulted in significant reduction in core body temperature. The mortality rate was significantly higher in the normothermic group (60%) than in the two hypothermic groups combined (7%) (p = 0.015) or in the severely hypothermic group (0%) (p = 0.023). Hypothermic animals had significantly lower levels of creatinine kinase, lactate dehydrogenase, and lactate in addition to a lower base deficit after shock. However, severely hypothermic animals required greater volumes of colloid infusion and whole blood transfusion to maintain our target systolic blood pressure and hemoglobin levels when compared with normothermic animals. We saw a strong trend toward decreased oxygen consumption with hypothermia. CONCLUSIONS: : In our porcine model, we found that simulating mild and severe levels of environmental hypothermia during early resuscitation after hemorrhage was associated with a significantly decreased mortality rate. Furthermore, markers of cellular stress and organ dysfunction, including lactate levels and the base deficit, were lower in hypothermic animals. Decreasing oxygen consumption with hypothermia may, in part, explain the protective effects observed with hypothermia.

Noninvasive tissue oxygen saturation measurements identify supply dependency.

BACKGROUND: Hemorrhagic shock can lead to multiple organ failure and death. We have previously shown that noninvasive measurement of tissue oxygen saturation (StO(2)) has predictive value for outcomes in patients suffering hemorrhagic shock. Our study objectives were twofold: (1) to compare invasive and noninvasive measurements of local and systemic tissue hemoglobin oxygenation and (2) to compare the effects of various physiologic conditions seen in patients in hemorrhagic shock on tissue hemoglobin oxygenation. MATERIALS AND METHODS: We studied pigs in controlled conditions mimicking shock induced by one of the following: hypothermia, isovolemic hemodilution, or manipulations of vascular tone. We obtained both invasive and noninvasive measurements in a hind limb of StO(2), tissue hemoglobin index, femoral artery and venous flows, blood pressures, temperature, pH, pO(2), pCO(2), oxygen saturation, lactate, hemoglobin, and base excess. In all cases, we measured baseline values in both experimental and control hind limbs. RESULTS: We found that tissue hemoglobin oxygenation did not vary significantly over relevant physiologic temperatures. Under all physiologic conditions tested, we found supply-dependent oxygen consumption at oxygen levels less than 7 mL O(2)/min/kg. Similarly, we found that local oxygen delivery in animals subjected to varying degrees of isovolemic hemodilution or altered vascular tone was correlated with supply-dependent oxygen consumption, as measured by local noninvasive StO(2). CONCLUSIONS: Noninvasive StO(2) measurements are valid and durable over a wide range of physiologic conditions and correlate with invasively-measured oxygen delivery.

Hyperbaric oxygen does not improve outcome in patients with necrotizing soft tissue infection.

BACKGROUND: Patients with necrotizing soft tissue infections (NSTIs) require prompt surgical debridement, appropriate intravenous antibiotics, and intensive support. Despite aggressive treatment, their mortality and morbidity rates remain high. The benefit of hyperbaric oxygen (HBO) as an adjunctive treatment is controversial. We investigated the effect of HBO in treating NSTIs. METHODS: We analyzed clinical data retrospectively for 78 patients with NSTIs: 30 patients at one center were treated with surgery, antibiotics, and supportive care; 48 patients at a different center received adjunctive HBO treatment. We compared the two groups in terms of demographic characteristics, risk factors, NSTI microbiology, and patient outcomes. To identify variables associated with higher mortality rates, we used logistic regression analysis. RESULTS: Demographic characteristics and risk factors were similar in the HBO and non-HBO groups. The mean patient age was 49.5 years; 37% of the patients were female, and 49% had diabetes mellitus. Patients underwent a mean of 3.0 excisional debridements. The median hospital length of stay was 16.5 days; the median duration of antibiotic use was 15.0 days. In 36% of patients, cultures were polymicrobial; group A Streptococcus was the organism most commonly isolated (28%). We identified no statistically significant differences in outcomes between the two groups. The mortality rate for the HBO group (8.3%) was lower, although not significantly different (p = 0.48), than that observed for the non-HBO group (13.3%). The number of debridements was greater in the HBO group (3.0; p = 0.03). The hospital length of stay and duration of antibiotic use were similar for the two groups. Multivariable analysis showed that hypotension on admission and immunosuppression were significant independent risk factors for death. CONCLUSIONS: Adjunctive use of HBO to treat NSTIs did not reduce the mortality rate, number of debridements, hospital length of stay, or duration of antibiotic use. Immunosupression and early hypotension were important risk factors associated with higher mortality rates in patients with NSTIs.

Collagen deposition limits immune reconstitution in the gut.

Despite suppression of human immunodeficiency virus (HIV) replication by antiretroviral therapy, reconstitution of CD4+ cells is variable and incomplete, particularly in gut-associated lymphatic tissues (GALT). We have previously shown that immune activation and inflammation in HIV-infected and simian immunodeficiency virus-infected lymph nodes results in collagen deposition and disruption of the lymphatic tissue architecture, and this damage contributes to CD4+ cell depletion before treatment and affects the extent of immune reconstitution after treatment. In the present study, we compared collagen deposition and the extent of depletion and reconstitution of total CD4+ cells and subsets in peripheral blood, lymph nodes, and inductive and effector sites in GALT. We show that CD4+ cell depletion in GALT correlates with the rapidity and greater magnitude of collagen deposition in this compartment, compared with that in peripheral lymph nodes, and that although treatment does not restore CD4+ cells to effector sites, treatment in the early stages of infection can increase CD4+ central memory cells in Peyer patches.

Aggressive red blood cell transfusion: no association with improved outcomes for victims of isolated traumatic brain injury.

BACKGROUND: Clinical studies have caused blood transfusion practices in critically ill patients to become more conservative in the last decade. However, few studies have focused on trauma patients, particularly those with severe isolated traumatic brain injury. METHODS: We conducted a retrospective study to test the hypothesis that patients with severe brain injury would not benefit from aggressive red blood cell transfusion (RBCT). End points of the study were in-hospital mortality and morbidity (pneumonia, urinary tract infection, deep venous thrombosis, pulmonary embolus, decubitus ulcer, bacteremia, septic shock, myocardial infarction, and seizure). Included in our retrospective study were patients at two urban, level I trauma centers who were admitted with a diagnosis of isolated head injury and with a Glasgow Coma Scale (GCS) score of 8 or less. We recorded demographic, interventional, and outcome variables. RESULTS: In 289 patients, 24 of 25 (96%) were transfused if their lowest recorded intensive care unit (ICU) hemoglobin level was 8.0 g/dl or less. In contrast, only 9/182 (5%) of these 289 patients were transfused if the hemoglobin levels were 10.0 g/dl or greater. In the remaining 82 patients with lowest ICU hemoglobin levels of 8.0-10.0 g/dl, 52% were transfused. These 82 patients (43 underwent RBCT and 39 did not) were included in our analysis. DISCUSSION: The overall in-hospital mortality rate was 32%; rates were similar between the two groups (29%, non-RBCT; 35%, RBCT) (P = 0.64). Likewise, in-hospital morbidity was similar between groups. Logistic and proportional hazard regression analyses identified RBCT as one predictor of mortality. CONCLUSIONS: Our results suggest that a restrictive transfusion practice is safe for severely head-injured patients.

Eight hours of hypotensive versus normotensive resuscitation in a porcine model of controlled hemorrhagic shock.

OBJECTIVES: The aim of this study was to compare hypotensive and normotensive resuscitation in a porcine model of hemorrhagic shock. METHODS: This was a prospective, comparative, randomized survival study of controlled hemorrhagic shock using 28 male Yorkshire-Landrace pigs (15 to 25 kg). In 24 splenectomized pigs, the authors induced hemorrhagic shock to a systolic blood pressure (sBP) of 48 to 58 mm Hg (approximately 35% bleed). Pigs were randomized to undergo normotensive resuscitation (sBP of 90 mm Hg, n = 7), mild hypotensive resuscitation (sBP of 80 mm Hg, n = 7), severe hypotensive resuscitation (sBP of 65 mm Hg, n = 6), or no resuscitation (n = 4). The authors also included a sham group of animals that were instrumented and splenectomized, but that did not undergo hemorrhagic shock (n = 4). After the initial 8 hours of randomized pressure-targeted resuscitation, all animals were resuscitated to a sBP of 90 mm Hg for 16 hours. RESULTS: Animals that underwent severe hypotensive resuscitation were less likely to survive, compared with animals that underwent normotensive resuscitation. Mean arterial pressure (MAP) decreased with hemorrhage and increased appropriately with pressure-targeted resuscitation. Base excess (BE) and tissue oxygen saturation (StO2) decreased in all animals that underwent hemorrhagic shock. This decrease persisted only in animals that were pressure target resuscitated to a sBP of 65 mm Hg. CONCLUSIONS: In this model of controlled hemorrhagic shock, initial severe hypotensive pressure-targeted resuscitation for 8 hours was associated with an increased mortality rate and led to a persistent base deficit (BD) and to decreased StO2, suggesting persistent metabolic stress and tissue hypoxia. However, mild hypotensive resuscitation did not lead to a persistent BD or to decreased StO2, suggesting less metabolic stress and less tissue hypoxia.