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April 2002


Rapid (0.5 degrees C/min) minimally invasive induction of hypothermia using cold perfluorochemical lung lavage in dogs.

OBJECTIVE: Demonstrate minimally invasive rapid body core and brain cooling in a large animal model. DESIGN: Prospective controlled animal trial. SETTING: Private research laboratory. SUBJECTS: Adult dogs, anesthetized, mechanically ventilated. INTERVENTIONS: Cyclic lung lavage with FC-75 perfluorochemical (PFC) was administered through a dual-lumen endotracheal system in the new technique of ‘gas/liquid ventilation’ (GLV). In Trial-I, lavage volume (V-lav) was 19 ml/kg, infused and withdrawn over a cycle period (tc) of 37 s. (effective lavage rate V’-lav=31 ml/kg/min.) Five dogs received cold (approximately 4 degrees C) PFC; two controls received isothermic PFC. In Trial-II, five dogs received GLV at V-lav=8.8 ml/kg, tc=16 s, V’-lav=36 ml/kg/min. MEASUREMENTS AND MAIN RESULTS: Trial-I tympanic temperature change was -3.7+/-0.6 degrees C (SD) at 7.5 min, reaching -7.3+/-0.6 degrees C at 18 min. Heat transfer efficiency was 60%. In Trial-II, efficiency fell to 40%, but heat-exchange dead space (VDtherm) remained constant. Lung/blood thermal equilibration half-time was <8 s. Isothermic GLV caused hypercapnia unless gas ventilation was increased. At necropsy after euthanasia (24 h), modest lung injury was seen. CONCLUSIONS: GLV cooling times are comparable to those for cardiopulmonary bypass. Heat and CO(2) removal can be independently controlled by changing the mix of lavage and gas ventilation. Due to VDtherm of approximately 6 ml/kg in dogs, efficient V-lav is >18 ml/kg. GLV cooling power appears more limited by PFC flows than lavage residence times. Concurrent gas ventilation may mitigate heat-diffusion limitations in liquid breathing, perhaps via bubble-induced turbulence.

Resuscitation 2001 Aug;50(2):189-204

Hypothermia after cardiac arrest: feasibility and safety of an external cooling protocol.

BACKGROUND: No proven neuroprotective treatment exists for ischemic brain injury after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in animal models. METHODS AND RESULTS: A safety and feasibility trial was designed to evaluate mild-to-moderate induced hypothermia by use of external cooling blankets after cardiac arrest. Inclusion criteria were return of spontaneous circulation within 60 minutes of advanced cardiac life support, hypothermia initiated within 90 minutes, persistent coma and lack of acute myocardial infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained for 24 hours followed by passive rewarming. Nine patients were prospectively enrolled. Mean time from advanced cardiac life support to return of spontaneous circulation was 11 minutes (range 3 to 30); advanced cardiac life support to initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1 had partial neurological recovery. One patient developed unstable cardiac dysrhythmia. No other unexpected complications occurred. CONCLUSIONS: Mild-to-moderate induced hypothermia after cardiac arrest is feasible and safe. However, external cooling is slow and imprecise. Efforts to speed the start of cooling and to improve the cooling process are needed.

Circulation 2001 Oct 9;104(15):1799-804

Post-resuscitative hypothermic bypass reduces ischemic brain injury in swine.

OBJECTIVES: Increasing human and laboratory evidence suggests that post-resuscitative brain hypothermia reduces the pathologic consequences of brain ischemia. Using a swine model of prolonged cardiac arrest, this investigation sought to determine whether unilateral hypothermic carotid bypass was capable of inducing selective brain hypothermia and reducing neurohistologic damage. METHODS: Ventricular fibrillation was induced in common swine (n = 12). After 20 minutes of cardiopulmonary arrest (without ventilatory support or cardiopulmonary resuscitation), systemic extracorporeal bypass was instituted to restore coronary and cerebral perfusion, followed by restoration of normal sinus rhythm. Animals randomized to the normal brain temperature (NBT) cohort received mechanical ventilation and intravenous fluids for 24 hours. The selective brain hypothermia (SBH) cohort received 12 hours of femoral/carotid bypass at 32 degrees C. The bypass temperature was then increased one degree per hour until reaching 37 degrees C and continued at this temperature until completion of the protocol (24 hours). Histopathologic damage was evaluated in two areas of the hippocampus. RESULTS: Normal sinus rhythm was restored in all animals after the systemic (femoral/femoral) bypass was initiated. Nasal temperature (surrogate measure of brain temperature) remained higher than 37.0 degrees C throughout the 24-hour recovery period in the NBT animals. In the SBH cohort, right nasal temperature dropped to the mild hypothermic range (<34 degrees C) two hours after institution of femoral/carotid bypass. This was maintained throughout the 12-hour cooling period without hemodynamic compromise. There was a significant improvement in the neurohistology scores in the CA1 region of the hippocampus of the SBH treated animals as compared with those of the NBT cohort. CONCLUSIONS: Post-resuscitative selective brain hypothermia reduced regional ischemic brain damage in swine with prolonged ventricular fibrillation.

Acad Emerg Med 2001 Oct;8(10):937-45

Rapid development of brain hypothermia using femoral-carotid bypass.

OBJECTIVES: Advances in the field of cardiopulmonary resuscitation have led to an increasing number of patients initially surviving sudden cardiac arrest. Unfortunately, most of these patients do not recover from the resultant anoxic brain insult. Several animal and human trials have suggested that post-resuscitative brain hypothermia may improve neurologic recovery after cardiopulmonary arrest. Present cooling methods are slow, induce only brain surface cooling, or result in systemic hypothermia. The authors tested the hypothesis that unilateral hypothermic carotid bypass would induce bilateral brain cooling without evoking systemic hypothermia or hemodynamic instability. METHODS: Anesthetized, ventilated common swine (n = 6, 24-37 kg) underwent right femoral and carotid artery bypass cannulation. Central and peripheral hemodynamic parameters were recorded every 2 minutes throughout the procedure. Thermodynamic parameters included bilateral frontal lobe, bilateral nasopharyngeal, pulmonary artery, and rectal temperatures. Hypothermic femoral-carotid bypass was accomplished by drawing blood from the right femoral artery, cooling it to 24 degrees C, and returning it to the right carotid artery at a flow rate of 5 mL/kg/min for 30 minutes. RESULTS: With initiation of cooling, brain temperatures dropped rapidly from baseline of 37.2 degrees C to 30.6 degrees C (right frontal lobe) and 33.1 degrees C (left frontal lobe) at 30 minutes. Pulmonary artery and rectal temperatures also decreased, but never reached mild hypothermic levels (34 degrees C). There was no significant change in any hemodynamic parameters during brain cooling. CONCLUSIONS: Femoral-carotid hypothermic bypass rapidly induced a state of selective brain hypothermia without causing systemic hypothermia or hemodynamic instability.

Acad Emerg Med 2001 Apr;8(4):303-8

Hypothermia and hyperthermia in children after resuscitation from cardiac arrest.

OBJECTIVE: In experimental models of ischemic-anoxic brain injury, changes in body temperature after the insult have a profound influence on neurologic outcome. Specifically, hypothermia ameliorates whereas hyperthermia exacerbates neurologic injury. Accordingly, we sought to determine the temperature changes occurring in children after resuscitation from cardiac arrest. STUDY DESIGN: The clinical records of 13 children resuscitated from cardiac arrest were analyzed. Patients were identified through the emergency department and pediatric intensive care unit arrest logs. Only patients surviving for > or =12 hours after resuscitation were considered for analysis. Charts were reviewed for body temperatures, warming or cooling interventions, antipyretic and antimicrobial administration, and evidence of infection. RESULTS: Seven patients had a minimum temperature (T min) of < or =35 degrees C and 11 had a maximum temperature (T max) of > or =38.1 degrees C. Hypothermia often preceded hyperthermia. All 7 patients with T min < or =35 degrees C were actively warmed with heating lamps and 5 of 7 responded to warming with a rebound of body temperatures > or =38.1 degrees C. None of the 6 patients with T min >35 degrees C were actively warmed but all developed T max > or =38.1 degrees C. Six patients received antipyretics and 11 received antibiotics. Fever was not associated with a positive culture in any case. Conclusion. Spontaneous hypothermia followed by hyperthermia is common after resuscitation from cardiac arrest. Temperature should be closely monitored after cardiac arrest and fever should be managed expectantly.

Pediatrics 2000 Jul;106(1 Pt 1):118-22

Cerebral hypothermia for prevention of brain injury following perinatal asphyxia.

The possibility that hypothermia has a therapeutic role during or after resuscitation from severe perinatal asphyxia has been a longstanding focus of research. Early studies using short periods of cooling had limited and contradictory results. We now know that resuscitation can be followed by a “latent” phase, characterized by transient recovery of cerebral energy metabolism, before secondary deterioration occurs with seizures, cytotoxic edema and cerebral energy failure 6 to 15 hours after birth. Recent experimental studies have shown that moderate cerebral hypothermia initiated as soon as possible in the latent phase, before the onset of secondary injury, and continued for 48 hours or more is associated with potent, long-lasting neuroprotection. These encouraging results must be balanced against the well-known adverse systemic effects of hypothermia. Randomized clinical trials are in progress to test the safety and efficacy of cerebral hypothermia.

Curr Opin Pediatr 2000 Apr;12(2):111-5

Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest. A clinical feasibility trial. Hypothermia after cardiac arrest (HACA) study group.

BACKGROUND AND PURPOSE: Recent animal studies showed that mild resuscitative hypothermia improves neurological outcome when applied after cardiac arrest. In a 3-year randomized, prospective, multicenter clinical trial, we hypothesized that mild resuscitative cerebral hypothermia (32 degrees C to 34 degrees C core temperature) would improve neurological outcome after cardiac arrest. METHODS: We lowered patients’ temperature after admission to the emergency department and continued cooling for at least 24 hours after arrest in conjunction with advanced cardiac life support. The cooling technique chosen was external head and total body cooling with a cooling device in conjunction with a blanket and a mattress. Infrared tympanic thermometry was monitored before a central pulmonary artery thermistor probe was inserted. RESULTS: In 27 patients (age 58 [interquartile range [IQR] 52 to 64] years; 7 women; estimated “no-flow” duration 6 [IQR 1 to 11] minutes and “low-flow” duration 15 [IQR 9 to 23] minutes; admitted to the emergency department 36 [IQR 24 to 43] minutes after return of spontaneous circulation), we could initiate cooling within 62 (IQR 41 to 75) minutes and achieve a pulmonary artery temperature of 33+/-1 degrees C 287 (IQR 42 to 401) minutes after cardiac arrest. During 24 hours of mild resuscitative hypothermia, no major complications occurred. Passive rewarming >35 degrees C was accomplished within 7 hours. CONCLUSIONS: Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states.

Stroke 2000 Jan;31(1):86-94

Recovery of a 62-year-old man from prolonged cold water submersion.

Recovery from prolonged cold water submersion is well documented in children but rare in adults. In the few adult cases reported, significant body cooling occurred (rectal temperature ranging from 22 degrees to 32 degrees C) and the victims were relatively young (< 40 years). We report a case of a 62-year-old man who was submersed in 2 degrees to 3 degrees C water for 15 minutes (time from initial submersion to intubation = 22 minutes). At the time of rescue, he had no vital signs, received prehospital Advanced Life Support, and was transported to hospital. On arrival at hospital, the patient remained in full cardiopulmonary arrest with an agonal ECG rhythm and had an initial pH of 6.77. Initial rectal temperature was near normal (36 degrees C) but subsequently dropped to 33 degrees C. The patient was resuscitated, rewarmed by forced-air warming, and treated for acute myocardial infarction, pulmonary edema and generalized seizures. He was discharged after 27 days with minor neurologic abnormalities. Given the near-normal initial rectal temperature, preferential brain cooling may have been at least partially responsible for the positive neurologic outcome.

Ann Emerg Med 1998 Jan;31(1):127-31

Study of mechanism of selective head cooling-dehydration combined therapy for brain resuscitation: effect on function of brain cellular membrane

We induced cerebral complete ischemia (CCI) by "four-vessel" model. The changes of Na+,K(+)-ATPase, Ca2+, Mg(2+)-ATPase, phospholipase A2 (PLA2), total phospholipids on brain cellular membrane (BCM) at 30, 180, 360 min of reperfusion following 30 min CCI were observed. The effects of selective head cooling (SHC, 28C, surface cooling method), mannitol dehydration (MD), and selective head cooling-dehydration combined therapy (SHCDCT) on these changes were also investigated. Compared with non-ischemic, during reperfusion activities of Na+, K(+)-ATPase, Ca2+, Mg(2+)-ATPase decreased while PLA2 increased (P < 0.001), phospholipids decreased at 180 and 360 min of reperfusion (P < 0.01). SHC and SHCDCT blocked all above changes, MD had no effect. These results suggest that SHCDCT after starting reperfusion do promote recruitment of BCM function by blockade of the successive reperfusion damage on BCM.

Zhonghua Wai Ke Za Zhi 1994 Nov;32(11):688-91

Thymic Protein A

Improved immune activation markers in chronic fatigue and immune dysfunction syndrome (CFIDS) patients treated with thymic protein A.

PURPOSE: To evaluate the effects of the orally administered thymic protein A on clinical blood parameters and the subjective symptoms common to patients with chronic fatigue and immune dysfunction syndrome (CFIDS). MATERIALS AND METHODS: A novel immune modulator, thymic protein A, in oral formulation was tested in 23 CFIDS patients manifesting clinical symptoms of CFIDS and abnormal CD8+ subpopulations and interferon pathway-associated enzyme levels. RESULTS: Sixteen of the 23 patients experienced normalization of immune function with a corresponding improvement in clinical symptoms of CFIDS. CONCLUSION: The data suggest that reinstitution of immune regulation with thymic protein A may ameliorate symptoms associated with CFIDS.

Journal of Nutritional & Environmental Medicine (2001) 11, 241-247