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Samuel A Tisherman

Publications and source records attributed to Samuel A Tisherman.

At least 19 recordsLinked to original sources
PubMed2007

Emergency preservation and delayed resuscitation allows normal recovery after exsanguination cardiac arrest in rats: a feasibility trial.

OBJECTIVE: Emergency preservation and resuscitation (EPR) comprise a novel approach for resuscitation of exsanguination cardiac arrest victims. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass. Development of a rat EPR model would enable study of the molecular mechanisms of neuronal injury and the screening of novel agents for emergency preservation. DESIGN: A prospective, randomized study. SETTING: University research facility. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Isoflurane-anesthetized rats were subjected to lethal hemorrhage (12.5 mL for 5 mins), followed by KCl-induced cardiac arrest and 1 min of no flow. Three groups (n=6) were studied: hypothermic EPR (H-EPR; 0 degrees C flush; target temperature, 15 degrees C); normothermic EPR (N-EPR; 38 degrees C flush); and controls. After 20 mins of H-EPR or N-EPR, resuscitation was initiated with cardiopulmonary bypass for 60 mins and mechanical ventilation. Controls were subjected to complete experimental preparation and anesthesia without cardiac arrest, followed by 60 mins of cardiopulmonary bypass and mechanical ventilation. Surviving rats were extubated 2 hrs later. Survival, Overall Performance Category (1, normal; 5, death), Neurologic Deficit Score, Histologic Damage Score, and biochemistry were assessed in survivors on day 7. MEASUREMENTS AND MAIN RESULTS: All rats in H-EPR and control groups survived, whereas none of the rats in the N-EPR group had restoration of spontaneous circulation. All rats in the H-EPR and control groups achieved Overall Performance Category 1, normal Neurologic Damage Score, and normal or near normal Histologic Damage Score and biochemical markers of organ injury. CONCLUSIONS: We have established an EPR model in rats showing no neurologic injury, despite an exsanguination cardiac arrest, followed by 20 mins of EPR using miniaturized cardiopulmonary bypass. Establishment of this model should facilitate application of molecular tools to study the effects of hypothermic preservation and reperfusion and to screen novel pharmacologic adjuncts.

Animals↗
PubMed2006

Small volume resuscitation with tempol is detrimental during uncontrolled hemorrhagic shock in rats.

BACKGROUND: In a previous study, titration of a hypertonic saline (HTS) solution during severe uncontrolled hemorrhagic shock (UHS) failed to reduce mortality. In a separate study, a novel antioxidant, polynitroxylated albumin (PNA) plus tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), infused during shock increased long-term survival. We hypothesized that combining potent antioxidants with a hypertonic solution during UHS would preserve the logistical advantage of small volume resuscitation and improve survival. METHODS: An UHS outcome model in rats was used. UHS phase I (90 min) included blood withdrawal of 30 ml/kg over 15 min, followed by tail amputation for uncontrolled bleeding. At 20 min, rats were randomized to four groups (n=10 each) for hypotensive resuscitation from 20 to 90 min (mean arterial pressure [MAP] > or = 40 mmHg): HTS/starch group received 7.2% NaCl/10% hydroxyethyl starch; HTS/albumin group received 7.5% NaCl/20% albumin; HTS/PNA group received 7.5% NaCl/20% PNA; HTS/albumin+tempol group received 7.5% NaCl/20% albumin plus tempol. Resuscitation phase II (180 min) included hemostasis, return of shed blood and administration of fluids to restore MAP > or = 80 mmHg. Observation phase III was to 72 h. RESULTS: The total amount of fluid required to maintain hypotensive MAP during HS was low and did not differ between groups (range: 3.4+/-1.9 to 5.3+/-2.5 ml/kg). The rate of fluid administration required was higher in the HTS/albumin+tempol group compared to all other groups (p=0.006). Additional uncontrolled blood loss was highest in the HTS/PNA group (16.2+/-5.7 ml/kg [p=0.01] versus 10.4+/-7.9 ml/kg in the HTS/starch group, 7.7+/-5.2 ml/kg in the HTS/albumin group and 8.2+/-7.1 ml/kg in the HTS/albumin+tempol group). MAP after start of resuscitation in phase I was lower in the HTS/albumin+tempol group than the HTS/albumin or HTS/PNA groups (p<0.01). This group was also less tachycardic. Long-term survival was low in all groups (2 of 10 after HTS/starch and 1 of 10 after HTS/albumin, 3 of 10 after HTS/PNA, 1 of 10 after HTS/albumin+tempol). Median survival time was shortest in the HTS/albumin+tempol group (72 min [CI 34-190]) compared to all other groups (p=0.01). CONCLUSIONS: Despite its benefits in other model systems, free tempol is potentially hazardous when combined with hypertonic fluids. PNA abrogates these deleterious effects on acute mortality but may lead to increased blood loss in the setting of UHS.

Albumins↗
PubMed2006

Induction of profound hypothermia for emergency preservation and resuscitation allows intact survival after cardiac arrest resulting from prolonged lethal hemorrhage and trauma in dogs.

BACKGROUND: Induction of profound hypothermia for emergency preservation and resuscitation (EPR) of trauma victims who experience exsanguination cardiac arrest may allow survival from otherwise-lethal injuries. Previously, we achieved intact survival of dogs from 2 hours of EPR after rapid hemorrhage. We tested the hypothesis that EPR would achieve good outcome if prolonged hemorrhage preceded cardiac arrest. METHODS AND RESULTS: Two minutes after cardiac arrest from prolonged hemorrhage and splenic transection, dogs were randomized into 3 groups (n=7 each): (1) the cardiopulmonary resuscitation (CPR) group, resuscitated with conventional CPR, and the (2) EPR-I and (3) EPR-II groups, both of which received 20 L of a 2 degrees C saline aortic flush to achieve a brain temperature of 10 degrees C to 15 degrees C. CPR or EPR lasted 60 minutes and was followed in all groups by a 2-hour resuscitation by cardiopulmonary bypass. Splenectomy was then performed. The CPR dogs were maintained at 38.0 degrees C. In the EPR groups, mild hypothermia (34 degrees C) was maintained for either 12 (EPR-I) or 36 (EPR-II) hours. Function and brain histology were evaluated 60 hours after rewarming in all dogs. Cardiac arrest occurred after 124+/-16 minutes of hemorrhage. In the CPR group, spontaneous circulation could not be restored without cardiopulmonary bypass; none survived. Twelve of 14 EPR dogs survived. Compared with the EPR-I group, the EPR-II group had better overall performance, final neurological deficit scores, and histological damage scores. CONCLUSIONS: EPR is superior to conventional CPR in facilitating normal recovery after cardiac arrest from trauma and prolonged hemorrhage. Prolonged mild hypothermia after EPR was critical for achieving intact neurological outcomes.

Animals↗
PubMed2006

Management of sepsis.

Severe sepsis remains a common cause of death in surgical patients. Eradication of the septic source and supportive care has long been the mainstay of treatment. In recent years, however, early goal-directed therapy, tighter glucose control, administration of drotrecogin alfa (activated), and steroid replacement have produced improved morbidity and mortality. In the future, a better understanding of the pathophysiology of sepsis and clinical studies may further improve outcomes from severe sepsis.

Critical Care↗
PubMed2006

Structure of surgical critical care and trauma fellowships.

INTRODUCTION: Surgical critical care (SCC) and trauma fellowships have developed in a variety of formats. Although SCC fellowships must meet specific requirements for accreditation by the Accreditation Council for Graduate Medical Education, trauma fellowships do not. As the American Board of Surgery is considering combining SCC, trauma, and emergency surgery into "acute care surgery" fellowship training, a better understanding of current program structures is needed. METHODS: The Education Committee of the Surgery Section of the Society of Critical Care Medicine sent surveys by e-mail to all SCC program directors. The survey included questions regarding the content of the fellowship, specifically, subspecialty rotations, trauma content, and operative experience. If they offered a trauma fellowship, the survey queried its structure also. RESULTS: A total of 39 of 82 surveys were returned. About one third of the programs have only SCC fellowships, one third combine SCC/trauma in 1-yr programs, and the remainder combine SCC/trauma in 2 yrs. Of the programs, 79% provided operative experience: 15% on a separate rotation and 39% on call during intensive care unit coverage. About half of the operative experiences were related to trauma and one quarter to emergency general surgery. The great majority of rotations were in general surgical or trauma intensive care units. CONCLUSION: SCC programs already include meaningful trauma and emergency general surgery operative experience. Surgical subspecialty intensive care unit and operative rotations may contribute to optimal training of the "acute care surgeon."

Critical Care↗
PubMed2005

Titrated hypertonic/hyperoncotic solution for hypotensive fluid resuscitation during uncontrolled hemorrhagic shock in rats.

BACKGROUND: In volume- or pressure-controlled hemorrhagic shock (HS) a bolus intravenous infusion of hypertonic/hyperoncotic solution (HHS) proved beneficial compared to isotonic crystalloid solutions. During uncontrolled HS in animals, however, HHS by bolus increased blood pressure unpredictably, and increased blood loss and mortality. We hypothesized that a titrated i.v. infusion of HHS, compared to titrated lactated Ringer's solution (LR), for hypotensive fluid resuscitation during uncontrolled HS reduces fluid requirement, does not increase blood loss, and improves survival. METHODS: We used our three-phased uncontrolled HS outcome model in rats. HS phase I began with blood withdrawal of 3 ml/100g over 15 min, followed by tail amputation. Then, hydroxyethyl starch 10% in NaCl 7.2% was given i.v. to the HHS group (n=10) and LR to the control group (n=10), both titrated to prevent mean arterial pressure (MAP) from falling below 40 mmHg during HS time 20-90 min. At HS 90 min, resuscitation phase II of 180 min began with hemostasis, return of all the blood initially shed, plus fluids i.v. as needed to maintain normotension (MAP>or=70 mmHg). Liver dysoxia was monitored as increase in liver surface pCO2 during phases I and II. Observation phase III was to 72 h. RESULTS: During HS, preventing a decrease in MAP below 40 mmHg required HHS 4.9+/-0.6 ml/kg (all data mean+/-S.E.M.), compared to LR 62.2+/-16.6 ml/kg (P<0.001), with no group difference in MAP. Uncontrolled blood loss during HS from the tail stump was 13.3+/-1.9 ml/kg with HHS infusion, versus 12.6+/-2.5 ml/kg with LR infusion (P=0.73). Serum sodium concentrations were moderately elevated at the end of HS in the HHS group (149+/-3 mmol/l) versus the LR group (139+/-1 mmol/l) (P=0.001), and remained elevated throughout. Liver pCO2 increased during HS in both groups equally (P<0.001 versus baseline), and tended to return to baseline levels at the end of HS. Blood gas and lactate values throughout did not differ between groups. During HS, 2 of 10 rats in the HHS group versus 0 of 10 in the LR group died (P=0.47). There was no difference between HHS and LR groups in survival rates to 72 h (3 of 10 in the HHS group versus 2 of 10 in the LR group) (P=1.0). Survival times, by life table analysis, were not different (P=0.75). CONCLUSION: In prolonged uncontrolled HS, a titrated i.v. infusion of HHS can maintain controlled hypotension with only one-tenth of the volume of LR required, without increasing blood loss. This titrated HHS strategy may not increase the chance of long-term survival.

Animals↗
PubMed2005

Admission hypothermia and outcome after major trauma.

OBJECTIVE: Uncontrolled exposure hypothermia is believed to be deleterious in the setting of major trauma. Prevention of hypothermia in the injured patient is currently practiced in both prehospital and in-hospital settings. However, this standard is based on studies of limited patient series that were not designed to identify the independent relationship between hypothermia and mortality. Recent studies suggest that therapeutically applied hypothermia may benefit selected patient subsets. The goal of this study was to evaluate the independent association between admission hypothermia and mortality after major trauma, with adjustment for clinical confounders. DESIGN: Retrospective analysis of a statewide trauma registry. The primary outcome was death at hospital discharge. The key exposure was hypothermia, defined as body temperature </=35 degrees C at admission. Multivariate regression was used to risk-adjust for age, severity and mechanism of injury, and route of temperature measurement. Additional adjustment for prehospital exposure time and intravenous fluid therapy was also evaluated. SETTING: Trauma centers of the Commonwealth of Pennsylvania. PATIENTS: All trauma patients >/=16 yrs of age for the years 2000-2002. Transferred patients were excluded. Patients were excluded if temperature or route of temperature measurement was not known. Both the full cohort and a subset with isolated severe head injury were evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 38,520 patients, 1,921 (5.0%) were hypothermic at admission. Admission hypothermia was independently associated with increased odds of death in both the full cohort (odds ratio, 3.03; 95% confidence interval, 2.62-3.51) and the subset with isolated severe head injury (2.21; 1.62-3.03), with adjustment for age, severity and mechanism of injury, and route of temperature measurement. CONCLUSIONS: Admission hypothermia is independently associated with increased adjusted odds of death after major trauma. The increase in mortality is not completely attributable to physiologic presentation or injury pattern or severity.

Adolescent↗
PubMed2005

Mild hypothermia improves survival after prolonged, traumatic hemorrhagic shock in pigs.

INTRODUCTION: Clinical studies have demonstrated improved survival after cardiac arrest with induction of mild hypothermia (34 degrees C). Infusion of ice-cold saline seems beneficial. The American Heart Association recommends therapeutic hypothermia for comatose survivors of cardiac arrest. For hemorrhagic shock (HS), laboratory studies suggest that mild hypothermia prolongs the golden hour for resuscitation. Yet, the effects of hypothermia during HS are unclear since retrospective clinical studies suggest that hypothermia is associated with increased mortality. Using a clinically relevant, large animal model with trauma and intensive care, we tested the hypothesis that mild hypothermia, induced with intravenous cold saline (ice cold or room temperature) and surface cooling, would improve survival after HS in pigs. METHODS: Pigs were prepared under isoflurane anesthesia. After laparotomy, venous blood (75 mL/kg) was continuously withdrawn over 3 hours (no systemic heparin). At HS 35 minutes, the spleen was transected. At HS 40 minutes, pigs were divided into three groups (n = 8, each): 1) Normothermia (Norm)(38 degrees C), induced with warmed saline; 2) Mild hypothermia (34 degrees C) induced with i.v. infusion of 2 degrees C saline (Hypo-Ice) and surface cooling; and 3) Mild hypothermia (34 degrees C), induced with room temperature (24 degrees C) i.v. saline (Hypo-Rm) and surface cooling. Fluids were given when mean arterial pressure (MAP) was <30 mmHg. At HS 3 hours, shed blood was returned and splenectomy was performed. Intensive care was continued to 24 hours. RESULTS: At 24 hours, there were two survivors in the Norm group, four in the Hypo-Ice group and seven in the Hypo-Rm group (p < 0.05 versus the Norm group, Log Rank). Time required to achieve 34 degrees C was 17 +/- 9 minutes in the Hypo-Ice group and 15 +/- 4 minutes in the Hypo-Rm group (NS). Compared with the Hypo-Rm group, the Hypo-Ice group required less saline during early HS (321 +/- 122 versus 571 +/- 184 mL, p < 0.05). The Hypo-Ice group also had higher lactate levels than the Hypo-Rm group (p < 0.05). Hypothermia did not cause any increase in bleeding compared with normothermia. CONCLUSION: Mild hypothermia during HS, induced by infusion of room temperature saline and surface cooling, improves survival in a clinically relevant model of HS and trauma. However, the use of iced saline in this model had detrimental effects and did not cool the animal more quickly than room temperature fluids. These findings suggest that optimal methods for induction of hypothermia need to be addressed for each potential indication, e.g. cardiac arrest versus HS.

Animals↗
PubMed2004

Suspended animation for resuscitation from exsanguinating hemorrhage.

In dogs, isotonic saline at 0-4 degrees C, flushed into the aorta at a rate of 1-2 L/min, with drainage of the vena cava, can achieve deep to profound hypothermia of vital organs at a cooling rate of up to 3 degrees C per minute. This achieves preservation of viability of the organism during predictable durations of no flow: cardiac arrest of 15-20 mins at Tty of 30-35 degrees C, cardiac arrest of 30 mins at Tty of 25 degrees C, cardiac arrest of 60 mins at Tty of 15 degrees C, and cardiac arrest of 90 mins at Tty of 10 degrees C. So far, pharmacologic approaches have not resulted in any breakthrough effect on outcome above that achieved with hypothermia, except perhaps the antioxidant tempol. Additional studies of novel drugs and, perhaps, combination therapies remain warranted. The optimal fluids to have in the circulation during circulatory arrest and reperfusions need to be determined. As laboratory studies to optimize suspended animation proceed, clinical trials should be initiated. In addition, devices should be developed to facilitate induction of suspended animation, eventually in the field.

Animals↗
PubMed2004

Mild hypothermia during prolonged cardiopulmonary cerebral resuscitation increases conscious survival in dogs.

OBJECTIVE: Therapeutic hypothermia during cardiac arrest and after restoration of spontaneous circulation enables intact survival after prolonged cardiopulmonary cerebral resuscitation (CPCR). The effect of cooling during CPCR is not known. We hypothesized that mild to moderate hypothermia during CPCR would increase the rate of neurologically intact survival after prolonged cardiac arrest in dogs. DESIGN: Randomized, controlled study using a clinically relevant cardiac arrest outcome model in dogs. SETTING: University research laboratory. SUBJECTS: Twenty-seven custom-bred hunting dogs (19-29 kg; three were excluded from outcome evaluation). INTERVENTIONS: Dogs were subjected to cardiac arrest no-flow of 3 mins, followed by 7 mins of basic life support and 10 mins of simulated unsuccessful advanced life support attempts. Another 20 mins of advanced life support continued with four treatments: In control group 1 (n = 7), CPCR was with normothermia; in group 2 (n = 6, 1 of 7 excluded), with moderate hypothermia via venovenous extracorporeal shunt cooling to tympanic temperature 27 degrees C; in group 3 (n = 6, 2 of 8 excluded), the same as group 2 but with mild hypothermia, that is, tympanic temperature 34 degrees C; and in group 4 (n = 5), with normothermic venovenous shunt. After 40 mins of ventricular fibrillation, reperfusion was with cardiopulmonary bypass for 4 hrs, including defibrillation to achieve spontaneous circulation. All dogs were maintained at mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs. Intensive care was to 96 hrs. MEASUREMENTS AND MAIN RESULTS: Overall performance categories and neurologic deficit scores were assessed from 24 to 96 hrs. Regional and total brain histologic damage scores and extracerebral organ damage were assessed at 96 hrs. In normothermic groups 1 and 4, all 12 dogs achieved spontaneous circulation but remained comatose and (except one) died within 58 hrs with multiple organ failure. In hypothermia groups 2 and 3, all 12 dogs survived to 96 hrs without gross extracerebral organ damage (p < .0001). In group 2, all but one dog achieved overall performance category 1 (normal); four of six dogs had no neurologic deficit and normal brain histology. In group 3, all dogs achieved good functional outcome with normal or near-normal brain histology. Myocardial damage scores were worse in the normothermic groups compared with both hypothermic groups (p < .01). CONCLUSION: Mild or moderate hypothermia during prolonged CPCR in dogs preserves viability of extracerebral organs and improves outcome.

Animals↗
PubMed2004

Hypothermia and injury.

PURPOSE OF REVIEW: Recent studies demonstrating that mild therapeutic hypothermia can improve the outcome from several ischemic and traumatic insults have led to increased interest in the potential benefits of hypothermia after injury. Previous clinical studies, however, have suggested that hypothermia is detrimental to trauma patients. This most likely is a result of differences in the physiologic effects between uncontrolled exposure hypothermia and controlled therapeutic hypothermia. The laboratory and clinical data regarding traumatic hemorrhagic shock and hypothermia are presented, as well as a novel approach to the patient with exsanguinating trauma: suspended animation. Therapeutic hypothermia for traumatic brain injury is discussed. RECENT FINDINGS: Laboratory studies of hemorrhagic shock demonstrate improved survival with mild hypothermia. For the first time, this was shown in a study in a large animal outcome model of hemorrhagic shock with trauma and intensive care. Because clinical studies continue to suggest an association between the development of hypothermia and worse outcomes in trauma patients, clinicians are continuing efforts to prevent and treat hypothermia. For exsanguination cardiac arrest, laboratory studies have demonstrated the feasibility of inducing hypothermic preservation via a rapid aortic flush (suspended animation). For traumatic brain injury, the most recent clinical trial did not show an overall benefit, but it seems that patients who arrive mildly hypothermic have better outcomes if hypothermia is maintained. SUMMARY: The dichotomy between laboratory findings that show a benefit of hypothermia and clinical findings that suggest detrimental effects remains difficult to explain. For now, preventing hypothermia remains prudent. Suspended animation seems promising for patients with exsanguinating trauma. Clinical trials of mild hypothermia during hemorrhagic shock and suspended animation for exsanguination are indicated. Clinical trials of hypothermia for traumatic brain injury are in progress.

Animals↗
PubMed2004

Suspended animation can allow survival without brain damage after traumatic exsanguination cardiac arrest of 60 minutes in dogs.

BACKGROUND: We have previously shown in dogs that exsanguination cardiac arrest of up to 120 minutes without trauma under profound hypothermia induced by aortic flush (suspended animation) can be survived without neurologic deficit. In the present study, the effects of major trauma (laparotomy, thoracotomy) are explored. This study is designed to better mimic the clinical scenario of an exsanguinating trauma victim, for whom suspended animation may buy time for resuscitative surgery and delayed resuscitation. METHODS: Fourteen dogs were exsanguinated over 5 minutes to cardiac arrest. Flush of saline at 2 degrees C into the femoral artery was initiated at 2 minutes of cardiac arrest and continued until a tympanic temperature of 10 degrees C was achieved. The dogs were then randomized into a control group without trauma (n = 6) or a trauma group (n = 8) that underwent a laparotomy and isolation of the spleen before hemorrhage and then, at the start of cardiac arrest, spleen transection and left thoracotomy. During cardiac arrest, splenectomy was performed. After 60 minutes of no-flow cardiac arrest, reperfusion with cardiopulmonary bypass was followed by intensive care to 72 hours. RESULTS: All 14 dogs survived to 72 hours with histologically normal brains. All control dogs were functionally neurologically intact. Four of eight trauma dogs were also functionally normal. Four had neurologic deficits, although three required prolonged mechanical ventilation because of airway edema and evidence of multiple organ failure. Blood loss from the chest and abdomen was variable and was associated with poor functional outcomes. CONCLUSION: Rapid induction of profound hypothermic suspended animation (tympanic temperature, 10 degrees C) can enable survival without brain damage after exsanguination cardiac arrest of 60 minutes even in the presence of trauma, although prolonged intensive care may be required. This technique may allow survival of exsanguinated trauma victims, who now have almost no chance of survival.

Abdominal Injuries↗
PubMed2003

Mild hypothermia during hemorrhagic shock in rats improves survival without significant effects on inflammatory responses.

OBJECTIVE: To explore the hypothesis that the survival benefit of mild, therapeutic hypothermia during hemorrhagic shock is associated with inhibition of lipid peroxidation and the acute inflammatory response. DESIGN: Prospective and randomized. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 +/- 0.5 degrees C) or mild hypothermia (33-34 degrees C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: All seven rats in the hypothermia group and seven of 15 rats in the normothermia group survived to 24 hrs (p <.05). Hypothermic rats had lower serum potassium and higher blood glucose concentrations at 90 mins of hemorrhagic shock (p <.05). At resuscitation time 24 hrs, the hypothermia group had less liver injury (based on serum concentrations of ornithine carbamolytransferase and liver histology) and higher blood glucose than the normothermia group (p <.05). There were no differences in serum free 8-isoprostane (a marker of lipid peroxidation by free radicals) between the two groups at either baseline or resuscitation time 1 hr. Serum concentrations of interleukin- 1 beta, interleukin-6, and tumor necrosis factor-alpha peaked at resuscitation time 1 hr. Tumor necrosis factor-alpha concentrations were higher (p <.05) at resuscitation time 1 hr in the hypothermia group compared with the normothermic group. Serum cytokine concentrations were not different between survivors and nonsurvivors in the normothermia group. Serum cytokine concentrations returned to baseline values in both groups by 24 hrs. There were no differences in the number of neutrophils in the lungs or the small intestine between the groups. More neutrophils were found in the lungs at resuscitation time 3 hrs than at resuscitation time 24 hrs in both groups (p <.01). CONCLUSIONS: These data suggest that lipid peroxidation and systemic inflammatory responses to hemorrhagic shock are minimally influenced by mild hypothermia, although liver injury is mitigated and survival improved. Other mechanisms of benefit from mild hypothermia need to be explored.

Animals↗
PubMed2003

Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia.

OBJECTIVES: This study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60-120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest. DESIGN: Prospective experimental comparison of three arrest times, without randomization. SETTING: University research laboratory. SUBJECTS: Twenty-seven custom-bred hunting dogs (17-25 kg). INTERVENTIONS: Dogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2 degrees C (at a rate of 1 L/min), until tympanic temperature reached 20 degrees C (for 60 mins of cardiac arrest), 15 degrees C (for 60 mins of cardiac arrest), or 10 degrees C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs. MEASUREMENTS AND MAIN RESULTS: We assessed overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0-40, mild; 40-100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20 degrees C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0-27%); and median total HDS, 28 (range, 4-36). Tympanic temperature of 15 degrees C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0-3%), and HDS 8 (0-48). Tympanic temperature 10 degrees C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2-18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10 degrees C was achieved after flush of 15 mins and resulted in all six dogs with OPC 1, NDS 0%, and HDS 8 (0-37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10 degrees C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22. CONCLUSIONS: In a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10 degrees C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest-which rarely can be resuscitated effectively with current methods-can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.

Animals↗