Body temperature in premature infants during the first week of life: Exploration using infrared thermal imaging.

BACKGROUND: Hypothermia is a problem for very premature infants after birth and leads to increased morbidity and mortality. Previously we found very premature infants exhibit abnormal thermal patterns, keeping foot temperatures warmer than abdominal temperatures for their first 12h of life. PURPOSE: We explored the utility of infrared thermography as a non-invasive method for measuring body temperature in premature infants in an attempt to regionally examine differential temperatures. RESULTS: Our use of infrared imaging to measure abdominal and foot temperature for extremely premature infants in heated, humid incubators was successful and in close agreement using Bland and Altman technique with temperatures measured by skin thermistors. CONCLUSIONS: Our study methods demonstrated that it was feasible to capture full body temperatures of extremely premature infants while they were resting in a heated, humid incubator using a Flir SC640 infrared camera. This technology offers researchers and clinicians a method to examine acute changes in perfusion differentials in premature infants which may lead to morbidity.

Teaching procedural skills to medical students: A pilot procedural skills lab.

BACKGROUND: Medical students have limited confidence in performing procedural skills. A pilot study was conducted to evaluate the effect of a multifaceted Procedural Skills Lab (PSL) on the confidence of medical students to perform procedural skills. METHODS: Twelve 2nd year medical students were randomly selected to participate in a pilot PSL. The PSL students met with an instructor for 2 h once a week for 4 weeks. Students participated in a flipped classroom and spaced education program before laboratory sessions that included a cadaver laboratory. Procedural skills included a focused assessment with sonography in trauma (FAST) scan, cardiac echocardiogram, lumbar puncture, arthrocentesis, and insertion of intraosseous and intravenous catheters. Students in the PSL were asked to rank their confidence in performing procedural skills before and after completion of the laboratory sessions (Wilcoxon ranked-sum test). A web-based questionnaire was also emailed to all 2nd year medical students to establish a baseline frequency for observing, performing, and confidence performing procedural skills (Mann-Whitney U-test). RESULTS: Fifty-nine percent (n = 106) of 180 2nd year medical students (n = 12 PSL students [treatment group], n = 94 [control group]) completed the survey. Frequency of observation, performance, and confidence in performing procedural skills was similar between the control and treatment groups at baseline. There was an increased confidence level (p < 0.001) for performing all procedural skills for the treatment group after completion of the PSL. DISCUSSION: An innovative PSL may increase students' confidence to perform procedural skills. Future studies will examine competency after a PSL.

Effect of a pharmacologically induced decrease in core temperature in rats resuscitated from cardiac arrest.

AIM: Hypothermia is recommended by international guidelines for treatment of unconscious survivors of cardiac arrest to improve neurologic outcomes. However, temperature management is often underutilized because it may be difficult to implement. The present study evaluated the efficacy of pharmacologically induced hypothermia on survival and neurological outcome in rats resuscitated from cardiac arrest. METHODS: Cardiac arrest was induced for 10 min in 120 rats. Sixty-one rats were resuscitated and randomized to normothermia, physical cooling or pharmacological hypothermia 5 min after resuscitation. Pharmacological hypothermia rats received a combination of ethanol, vasopressin and lidocaine (HBN-1). Physical hypothermia rats were cooled with intravenous iced saline and cooling pads. Rats in the pharmacological hypothermia group received HBN-1 at ambient temperature (20 °C). Normothermic rats were maintained at 37.3 ± 0.2 °C. RESULTS: HBN-1 (p < 0.0001) shortened the time (85 ± 71 min) to target temperature (33.5 °C) versus physical hypothermia (247 ± 142 min). The duration of hypothermia was 17.0 ± 6.8h in the HBN-1 group and 17.3 ± 7.5h in the physical hypothermia group (p = 0.918). Survival (p = 0.034), neurological deficit scores (p < 0.0001) and Morris Water Maze performance after resuscitation (p = 0.041) was improved in the HBN-1 versus the normothermic group. HBN-1 improved survival and early neurological outcome compared to the physical hypothermia group while there was no significant difference in performance in the Morris water maze. CONCLUSION: HBN-1 induced rapid and prolonged hypothermia improved survival with good neurological outcomes after cardiac arrest suggesting that pharmacologically induced regulated hypothermia may provide a practical alternative to physical cooling.

Putting class IIb recommendations to the test: the influence of unwitnessed and Non-VT/VF arrests on resource consumption and outcomes in therapeutic hypothermia and targeted temperature management.

Therapeutic hypothermia (TH) and targeted temperature management improve neurologic recovery, and survival for patients resuscitated from witnessed out-of-hospital ventricular tachycardia (VT) and ventricular fibrillation (VF) cardiac arrest. The American Heart Association recently gave a class IIb recommendation for the use of TH for non-VT/VF and unwitnessed arrests. We explored changes in baseline characteristics, resource use, and outcomes after expanding indications for TH at our institution based on these guidelines. Fifty-six consecutive patients treated with TH for out-of-hospital cardiac arrest were retrospectively evaluated based on whether they received treatment before (protocol 1) or after (protocol 2) broadening inclusion criteria. In protocol 1, TH was indicated after a witnessed VT/VF arrest. In protocol 2, TH was indicated for unwitnessed arrests, pulseless electrical activity, or asystole. Both populations undergoing TH had similarly extensive medical comorbidities and consumed considerable hospital resources. Overall, 64% of the patients from both protocols died in the hospital, although nominally lower mortality was seen in patients treated under protocol 1 compared with protocol 2 (59% vs. 67%, P = 0.57). Lower mortality was observed after VT/VF than after pulseless electrical activity or asystole (47% vs. 93% vs. 56%, P = 0.017). No patient survived following an unwitnessed arrest, and age (odds ratio per 10 years = 2.59; 95% confidence interval, 1.34-4.81) was independently associated with increased mortality. In an evolving field where best practice is still poorly defined, these data, along with future prospective studies in larger populations, should help to enhance care delivery and optimize cost-effectiveness strategies.

Brain resuscitation in the drowning victim.

Drowning is a leading cause of accidental death. Survivors may sustain severe neurologic morbidity. There is negligible research specific to brain injury in drowning making current clinical management non-specific to this disorder. This review represents an evidence-based consensus effort to provide recommendations for management and investigation of the drowning victim. Epidemiology, brain-oriented prehospital and intensive care, therapeutic hypothermia, neuroimaging/monitoring, biomarkers, and neuroresuscitative pharmacology are addressed. When cardiac arrest is present, chest compressions with rescue breathing are recommended due to the asphyxial insult. In the comatose patient with restoration of spontaneous circulation, hypoxemia and hyperoxemia should be avoided, hyperthermia treated, and induced hypothermia (32-34 °C) considered. Arterial hypotension/hypertension should be recognized and treated. Prevent hypoglycemia and treat hyperglycemia. Treat clinical seizures and consider treating non-convulsive status epilepticus. Serial neurologic examinations should be provided. Brain imaging and serial biomarker measurement may aid prognostication. Continuous electroencephalography and N20 somatosensory evoked potential monitoring may be considered. Serial biomarker measurement (e.g., neuron specific enolase) may aid prognostication. There is insufficient evidence to recommend use of any specific brain-oriented neuroresuscitative pharmacologic therapy other than that required to restore and maintain normal physiology. Following initial stabilization, victims should be transferred to centers with expertise in age-specific post-resuscitation neurocritical care. Care should be documented, reviewed, and quality improvement assessment performed. Preclinical research should focus on models of asphyxial cardiac arrest. Clinical research should focus on improved cardiopulmonary resuscitation, re-oxygenation/reperfusion strategies, therapeutic hypothermia, neuroprotection, neurorehabilitation, and consideration of drowning in advances made in treatment of other central nervous system disorders.

Induction of a prolonged hypothermic state by drug-induced reduction in the thermoregulatory set-point.

BACKGROUND: The marked improvement in outcome following induction of hypothermia after cardiac arrest has spurred the search for better methods to induce cooling. A regulated decrease in core temperature mediated by a drug-induced reduction in the set point for thermoregulation may be an ideal means of inducing hypothermia. To this end, the exploratory drug HBN-1 was assessed as a means to induce mild and prolonged hypothermia. METHODS: Free moving rats were infused i.v. for 12 hours with: a vehicle at room temperature (normothermia), a vehicle chilled to 4°C (forced hypothermia), or HBN-1 (mixture of ethanol, lidocaine, and vasopressin) at room temperature. Core (intra-abdominal) temperature (Tc) was measured telemetrically, tail skin temperature (Ttail) by infrared thermography, metabolic rate (MR) was estimated with indirect calorimetery, and shivering was scored visually. RESULTS: HBN-1 elicited a reduction in Tc from 37.5°C to 34°C within 80 minutes after initiation of the infusion; Tc was maintained between 33°C and 34°C for more than 13 hours. HBN-1 infusion was associated with a reduction in MR (p=0.0006), a slight reduction in Ttail, and no evidence of shivering (p<0.001). The forced hypothermia group displayed shivering (p<0.001), a significant increase in MR, and a decrease in Ttail, indicative of peripheral vasoconstriction to reduce heat loss. CONCLUSION: HBN-1 infusion induced a mild and prolonged hypothermia in free moving, unanesthetized rats characterized by modulation of thermoeffectors to reduce heat gain and increase heat loss. HBN-1 thus appears to elicit regulated hypothermia and may provide a new method for achieving a prolonged state of therapeutic hypothermia.

Drug-induced therapeutic hypothermia after asphyxial cardiac arrest in swine.

A feasibility study was performed to compare an investigational drug, HBN-1, to forced cooling to induce hypothermia after resuscitation in a translation model of asphyxial cardiac arrest in swine. Serum and cerebral spinal fluid neuron-specific enolase activity (sNSE and csfNSE) were measured after cardiac arrest as surrogate markers of brain injury. In a block design, swine resuscitated from 10 minutes of asphyxial cardiac arrest were infused intravenously with HBN-1 or iced saline vehicle (forced hypothermia [FH]) 5 to 45 minutes after return of spontaneous circulation (ROSC). External cooling in both groups was added 45 minutes after ROSC until hypothermia (T=4°C below baseline) was attained. Esophageal (core) temperature, shivering, cardiopulmonary parameters, and time to hypothermia after ROSC were monitored. sNSE and csfNSE were measured 180 minutes after ROSC. HBN-1 induced hypothermia significantly lowered temperature compared to FH 5-45 minutes after ROSC (p<0.0001). Time to hypothermia was reduced by HBN-1 (93±6 minutes) compared to FH (177±10 minutes) (p<0.0001). HBN-1 sNSE (0.7±1.9 ng/mL) and csfNSE (17.3±1.9 ng/mL) were lower compared to FH (6±1.6 ng/mL) and (49.7±32.0 ng/mL) (p<0.0001, p=0.022, respectively). There was no shivering with HBN-1 cooling while all FH cooled swine shivered (p<0.0001). The time to reach target hypothermia after cardiac arrest was reduced by nearly 50% with HBN-1 compared to the FH method of inducing hypothermia. Moreover, surrogate biomarkers of brain injury were significantly reduced with HBN-1 as compared to FH. While HBN-1-induced hypothermia shows promise for being neuroprotective, survival studies are needed to confirm these preliminary findings.

Nitroglycerin attenuates vasoconstriction of HBOC-201 during hemorrhagic shock resuscitation.

BACKGROUND: Vasoconstriction, an inherent property of Hemoglobin Based Oxygen Carriers (HBOC) potentially due to nitric oxide (NO) scavenging, may increase cardiovascular complications in HBOC resuscitated trauma patients. The purpose of this study was to determine if co-administration of a weak NO donor, intravenous nitroglycerin (NTG), with HBOC-201 during resuscitation from hemorrhagic shock could safely attenuate HBOC-201 vasoconstriction. METHODS AND RESULTS: Hemorrhagic shock was induced in 44 swine randomized to receive fluid resuscitation with HBOC, HBOC+NTG10 mcg/kg/min, HBOC+NTG20 mcg/kg/min, HBOC+NTG40 mcg/kg/min, Hetastarch (HES), HES+NTG20 mcg/kg/min, NTG20 mcg/kg/min and Lactated Ringers (LR). HBOC resuscitation from hemorrhagic shock increased mean arterial pressure (MAP=94+/-33 mmHg), mean pulmonary artery pressure (MPAP=29+/-11 mmHg) and systemic vascular resistance (SVR=2684+/-871 dyns/cm(5)) in comparison to HES. Co-administration of NTG during HBOC resuscitation attenuated vasoconstriction with HBOC+40 mcg/kg/min demonstrating the most robust reduction in vasoconstriction (MAP=59+/-23 mmHg, MPAP=18+/-7 mmHg, and SVR=1827+/-511 dyns/cm(5)), although the effects were transient. Co-administration of NTG with HBOC did not alter base deficit, lactate, methemoglobin levels, nor cause profound hypotension during resuscitation. CONCLUSION: Nitroglycerin attenuates vasoconstrictive properties of HBOC when co-administered during resuscitation in this swine model of hemorrhagic shock. Translational survival studies are required to determine if this strategy of attenuation of the vasoconstriction of HBOC-201 reduces cardiovascular complications and improves outcome with HBOC fluid resuscitation for hemorrhagic shock.

Independence of brain and trunk temperature during hypothermic preconditioning in rats.

UNLABELLED: Hypothermic preconditioning is rapid cooling and warming to induce tolerance to ischemia. The purpose of the study was to examine differences in brain and trunk temperature during hypothermic preconditioning. METHODS: Rats (n=18) were implanted with telemetric probes for simultaneous measure of brain and trunk temperature. Hypothermic preconditioning was produced by exposing rats to cool and warm environments that produced rapid cooling to 30 degrees C and warming to 35 degrees C. RESULTS: Brain temperature was warmer (37.56+/-0.45 degrees C) than trunk (37.17+/-0.29 degrees C) temperature in unanesthetized, free roaming rats at room temperature (t-test p=0.04). The brain cooled (0.59+/-0.1 degrees C/min) quicker than the trunk (0.44+/-0.19 degrees C/min) during cooling cycles of hypothermic preconditioning and the brain (0.28+/-0.04 degrees C/min) warmed quicker than the trunk (0.18+/-0.07 degrees C/min) during the warming cycle of hypothermic preconditioning (t-test p<0.0001). When the trunk temperature probe was designated to reach the target temperature of 35 degrees C during warming, the brain temperature (38.1+/-0.44 degrees C) was warmer than trunk temperature (34.95+/-0.16 degrees C) during the peak of warming (t-test p<0.0001). CONCLUSION: The brain cools and warms quicker than the trunk during hypothermic preconditioning. Failure to anticipate these differences could lead to unrecognized brain hyperthermia during warming. Appreciation of differences in rates of change between brain and trunk temperature may be important when designing hypothermic preconditioning experiments.

VOXEL-WISE GROUP ANALYSIS OF DTI.

Diffusion tensor MRI (DTI) is now a widely used modality to investigate the fiber tissues in vivo, especially the white matter in brain. An automatic pipeline is described in this paper to conduct a localized voxel-wise multiple-subject group comparison study of DTI. The pipeline consists of 3 steps: 1) Preprocessing, including image format converting, image quality check, eddy-current and motion artifact correction, skull stripping and tensor image estimation, 2) study-specific unbiased DTI atlas computation via affine followed by fluid nonlinear registration and warping of all individual DTI images into the common atlas space to achieve voxel-wise correspondence, 3) voxelwise statistical analysis via heterogeneous linear regression and wild bootstrap technique for correcting for multiple comparisons. This pipeline was applied to process data from a fitness and aging study and preliminary results are presented. The results show that this fully automatic pipeline is suitable for voxel-wise group DTI analysis.

Exercise and the aging mind: buffing the baby boomer's body and brain.

Among the fears of aging are loss of memory, cognitive decline, and loss of independence. Baby boomers have entered the "aged" cohort and are actively seeking ways to maintain strong bodies and strong minds. Bench to clinical research suggests that keeping physically active and engaged in moderate to vigorous exercise may be vital to brain health. Because exercise promotes neurogenesis, increased brain volume, and improved cognitive function, it can help the aging brain to retain plasticity. However the precise mechanisms by which exercise accomplishes these changes in the brain are not clearly understood. This study argues that "what is good for the heart is good for the brain," although more research is needed to determine the optimal exercise prescription for brain health and successful cognitive aging.

Infrared imaging of trauma patients for detection of acute compartment syndrome of the leg.

OBJECTIVE: Early compartment syndrome is difficult to diagnose, and a delay in the diagnosis can result in amputation or death. Our objective was to explore the potential of infrared imaging, a portable and noninvasive technology, for detecting compartment syndrome in the legs of patients with multiple trauma. We hypothesized that development of compartment syndrome is associated with a reduction in surface temperature in the involved leg and that the temperature reduction can be detected by infrared imaging. DESIGN: Observational clinical study. SETTING: Level I trauma center between July 2006 and July 2007. PATIENTS: Trauma patients presenting to the emergency department. INTERVENTIONS: Average temperature of the anterior surface of the proximal and distal region of each leg was measured in the emergency department with a radiometrically calibrated, 320 x 240, uncooled microbolometer infrared camera. MEASUREMENTS AND MAIN RESULTS: The difference in surface temperature between the thigh and foot regions (thigh-foot index) of the legs in trauma patients was determined by investigators blinded to injury pattern using thermographic image analysis software. The diagnosis of compartment syndrome was made intraoperatively. Thermographic images from 164 patients were analyzed. Eleven patients developed compartment syndrome, and four of those patients had bilateral compartment syndrome. Legs that developed compartment syndrome had a greater difference in proximal vs. distal surface temperature (8.80 +/- 2.05 degrees C) vs. legs without compartment syndrome (1.22 +/- 0.88 degrees C) (analysis of variance p < .01). Patients who developed unilateral compartment syndrome had a greater proximal vs. distal temperature difference in the leg with (8.57 +/- 2.37 degrees C) vs. the contralateral leg without (1.80 +/- 1.60 degrees C) development of compartment syndrome (analysis of variance p < .01). CONCLUSIONS: Infrared imaging detected a difference in surface temperature between the proximal and distal leg of patients who developed compartment syndrome. This technology holds promise as a supportive tool for the early detection of acute compartment syndrome in trauma patients.

Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation.

Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. deltaPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted deltaPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced deltaPKC translocation and increased its cleavage at 3 h of reperfusion. Since deltaPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either deltaPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of deltaPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote deltaPKC translocation/cleavage.

Mild cardiopulmonary arrest promotes synaptic dysfunction in rat hippocampus.

Cardiac arrest (CA) patients exhibit learning and memory disabilities. These deficits suggest that synaptic dysfunction may underlie such disabilities. The hypothesis of the present study was that synaptic dysfunction occurs following CA and that this precedes cell death. To test this hypothesis, we used histopathological and electrophysiological markers in the hippocampus of rats subjected to CA. Evoked potentials (EP) were determined in the CA1 region of hippocampal slices harvested from animals subjected to CA or sham-operated rats by stimulating the Schaffer collaterals and recording in the CA1 pyramidal region. EP amplitudes were significantly attenuated by approximately 60% in hippocampal slices harvested from animals subjected to CA. Hippocampal slices harvested from sham rats exhibited normal long-term potentiation (LTP). In contrast, hippocampal slices harvested 24 h after CA exhibited no LTP response, even when no histopathological abnormalities were observed. These data suggest that synaptic dysfunction occurs before and without overt histopathology. We suggest that the synaptic dysfunction precedes and may be an early marker for delayed neuronal cell death in the hippocampus after CA.

Infrared thermography: a rapid, portable, and accurate technique to detect experimental pneumothorax.

RATIONALE AND OBJECTIVE: Pneumothorax (Ptx) is a life-threatening complication that can result from trauma, mechanical ventilation, and invasive procedures. Infrared thermography (IRT), a compact and portable technology, has become highly sensitive. We hypothesized that IRT could detect Ptx by identifying associated changes in skin temperature. MATERIALS AND METHODS: Bilateral nonpenetrating chest incisions or needle punctures were performed in 21 anesthetized rats. Rats were then randomized to no, bilateral, left, or right Ptx by either open (n = 16) or closed percutaneous (n = 5) puncture through selected pleurae. Real-time thermographic images and surface temperature data were acquired with a noncooled infrared camera. RESULTS: In all cases, blinded observers correctly identified each Ptx with real-time grayscale image analysis. When compared to either the ipsilateral baseline or an abdominal reference, experimental Ptx produced a significantly greater decrease in surface temperature when compared to non-Ptx control. CONCLUSIONS: These results demonstrate that portable infrared imaging can rapidly and accurately detect changes in thoracic surface temperature associated with experimental pneumothorax.

Regulated hypothermia reduces brain oxidative stress after hypoxic-ischemia.

UNLABELLED: Regulated hypothermia produces a decrease in core temperature by lowering the brain's temperature set-point while maintaining thermoregulation at that lower set point. In contrast, forced hypothermia lowers core temperature by overwhelming the body's capacity to thermoregulate, but does not change the set-point. Regulated hypothermia has been shown to be cerebral protective in hibernating mammals. The effect of regulated hypothermia on the brain during reperfusion from hypoxic-ischemia has not been well studied. We induced regulated hypothermia with a neurotensin analogue (NT77) to determine whether it could reduce oxidative stress in the brain during reperfusion from asphyxial cardiac arrest (ACA) in rats. Mild hypothermia (32-34 degrees C) was induced by brief (4 h) external cooling (BC), NT77 or prolonged external cooling (24 h) (PC) 30 min after resuscitation from 8 min of ACA in rats. Malondialdehyde (MDA) levels in the brain were measured during reperfusion to quantitate oxidative stress. RESULTS: MDA levels in the hippocampus were elevated at 16 h of normothermic reperfusion versus 48 h with BC reperfusion. There was no increase in hippocampal MDA levels in the NT77 and PC groups at 24-72 h of reperfusion. Regulated hypothermia induced by NT77 reduced oxidative stress in the hippocampus during reperfusion from hypoxic-ischemia in comparison to forced brief external cooling of the same duration. In addition, the duration of external cooling after resuscitation also alters oxidative stress in the brain during reperfusion.

Neurotensin-induced hypothermia improves neurologic outcome after hypoxic-ischemia.

OBJECTIVE: External cooling is commonly used to force induction of mild hypothermia but requires equipment, has a slow onset of action, and must be prolonged to provide permanent neurologic benefits after hypoxic-ischemia. It is unknown whether the method for inducing mild hypothermia affects neurologic outcome after near-drowning. The objective of the study was to induce mild hypothermia with neurotensin analog NT77 or external cooling in a rat model of near-drowning. We hypothesize that NT77 would be more effective for improving neurologic outcome than external cooling of the same duration. DESIGN: Rats were randomized to a normothermic control, neurotensin-induced hypothermia, brief external cooling, or prolonged external cooling group after asphyxial cardiac arrest. SETTING: Laboratory investigation. SUBJECTS: Forty-eight rats. INTERVENTIONS: Mild hypothermia was induced by external cooling for 4 hrs (brief external cooling) or 24 hrs (prolonged external cooling) or by neurotensin-induced hypothermia administration 30 mins after asphyxial cardiac arrest in rats. MEASUREMENTS: Outcome was assessed by a neurologic deficit score, the Morris water maze, and CA1 hippocampus histology 15 days after resuscitation. MAIN RESULTS: Neurologic deficit score at 72 hrs after asphyxial cardiac arrest was lower with neurotensin-induced hypothermia (score, 0) and prolonged external cooling (score, 0) vs. normothermic control (score, 20) and brief external cooling (score, 18; p <.05). Latency time in the Morris water maze 15 days after asphyxial cardiac arrest was decreased with neurotensin-induced hypothermia (14+/-11 secs) and prolonged external cooling (18+/-9 secs) vs. normothermic control (74+/-17 secs) and brief external cooling (78+/-18 secs, p <.05). There was less ischemic neuronal damage with neurotensin-induced hypothermia (28+/-24%) and prolonged external cooling (21+/-14%) vs. normothermic control (61+/-32%) and brief external cooling (51+/-32%). CONCLUSIONS: Neurotensin-induced hypothermia improved neurologic outcome after asphyxial cardiac arrest in rats vs. brief external cooling but was comparable to prolonged external cooling.

HBOC-201 improves survival in a swine model of hemorrhagic shock and liver injury.

BACKGROUND: Blunt abdominal trauma that leads to hemorrhagic shock and cardiac arrest is almost always fatal in the prehospital setting. The current study investigated whether a hemoglobin-based oxygen carrier (HBOC-201) could maintain organ viability during an exsanguinating liver injury and allow for prolonged survival. This hypothesis was tested in a large animal model that simulated blunt abdominal trauma with major organ injury. METHODS: Swine underwent a liver crush, laceration and 50 ml/kg initial blood loss. The liver bled at 3 ml/kg per min during the resuscitation phase. No fluid (NF=6), hetastarch (HES=8), or HBOC-201 (HBOC=8) was given during the resuscitation phase. Swine alive 60 min after the initial injury underwent liver repair and 96 h observation. RESULTS: All HBOC swine survived 60 min versus none of the NF or HES swine (P<0.05). All HBOC swine survived 24 h and 7/8 survived 96 h with good functional recovery. CONCLUSIONS: HBOC resuscitation during liver bleeding in a swine model of hemorrhagic shock and liver injury allowed for 96 h survival. No fluid or HES in the same model was fatal.

Low-dose Carbicarb improves cerebral outcome after asphyxial cardiac arrest in rats.

STUDY OBJECTIVE: Controversy surrounds the use of buffers during cardiac arrest to correct acidosis. The objective of this study was to determine whether attenuation or neutralization of cerebral acidosis by Carbicarb alters hippocampal glutamate levels, neuronal cell death, and neurologic deficits after reperfusion from asphyxial cardiac arrest in rats. METHODS: Rats were prospectively randomized to either a control (n=45), low-dose Carbicarb (LDC; 3 mL/kg, n=45), or high-dose Carbicarb (HDC; 6 mL/kg, n=45) group in a blinded fashion during resuscitation after 8 minutes of asphyxial cardiac arrest. Microdialysis was used to assess brain pH and glutamate. A neurologic deficit score and neuronal cell death in the hippocampus were determined at day 7. RESULTS: Resuscitation was greatest in LDC rats (42/45) and least in HDC rats (28/45) versus that in control rats (34/45). Brain pH was higher in the LDC and HDC rats 10 minutes after resuscitation and remained higher than that of control rats for 120 minutes after resuscitation. Glutamate levels at 10 to 120 minutes after reperfusion were lowest in the LDC rats. LDC rats had the lowest neurologic deficit score (1+/-2) versus that of control rats (13+/-8) and HDC rats (19+/-6). Hippocampal neuronal cell death was lowest in LDC rats (30+/-20) versus that in control rats (86+/-47) and HDC rats (233+/-85). CONCLUSION: LDC administered during resuscitation from asphyxial cardiac arrest attenuated acidosis, improved resuscitation, and reduced neurologic deficits and the number of dead hippocampal neurons. Neutralization of cerebral acidosis with HDC increased the number of dead hippocampal neurons and neurologic deficits after resuscitation from cardiac arrest in rats.