Hirofumi Norio

Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest

The effects of mild hypothermia (MH) were investigated. From 1995 to 1996, 28 adult patients with out-of-hospital cardiopulmonary arrest (CPA) had return of spontaneous circulation and survived for more than two days. Thirteen patients were in the MH group. In the MH group, core temperature was maintained between 33 and 34 degrees C for 48 h, and then re-warmed to a temperature of 37 degrees C, at a rate of no greater than 1 degrees C per day. Fifteen patients, admitted before the MH protocol was instituted, were in the control group. Despite the fact that the number of witnessed arrests in the control group were greater than in the MH group, there were both more survivors (7/13 vs. 5/15) and more fully recovered patients (3/13 vs. 1/15) in the MH vs Control groups. Eleven of 13 MH patients, as compared to 6/15 controls developed pneumonia. Our study, although preliminary, suggests that MH might confer improved outcome, as has been shown in animal models, after CPA. This treatment is associated with an increase in pneumonic complications.

Effect of induced-hypothermia on short-term survival after volume-controlled hemorrhage in pigs

OBJECTIVE To examine whether induced hypothermia could prolong short-term survival after volume-controlled hemorrhagic shock (HS). MATERIALS AND METHODS Fifteen pigs with systemic heparin underwent blood withdrawal of 30 ml/kg over 15 min under spontaneous breathing with halothane anesthesia. The pigs were divided into three groups of five pigs each: Group 1, hemorrhage plus hypothermia with extracorporeal shunt circulation (ECSC); Group 2, hemorrhage plus normothermia with ECSC; and Group 3, hemorrhage alone. For Groups 1 and 2, arteriovenous ECSC was performed for 20 min during HS. The re-infused shunt blood was cooled down to approximately 15 degrees C in Group 1, whereas it was returned at 37.5 degrees C in Group 2. The pigs in Group 3 had no ECSC and were left at room temperature. All pigs were observed until their death or for a maximum of 240 min. RESULTS The mean pulmonary artery temperature (T(pa)) of Group 1 animals decreased to 34.5 degrees C at 15 min after the initiation of ECSC, and thereafter remained at 35.5 degrees C after undergoing ECSC. The T(pa) values for Groups 2 and 3 animals remained at 37.5 degrees C throughout the experiment. All five pigs in Group 1 survived until 240 min, whereas all pigs in Group 2 and 3 of five pigs in Group 3 died before 215 min after blood withdrawal. A life table analysis revealed significantly increased survival in Group 1 compared with Group 2 (P<0.01) and Group 3 (P<0.05). CONCLUSIONS In lightly anesthetized pigs during volume-controlled HS, induced hypothermia may prolong their short-term survival for reasons that remain to be clarified.

Mild hypothermia prolongs the survival time during uncontrolled hemorrhagic shock in rats

OBJECTIVE To test our hypothesis that during lethal uncontrolled hemorrhagic shock (UHS) in rats, mild hypothermia of either 36 or 34 degrees C would prolong the survival time in comparison with normotherma of 38 degrees C. METHODS Twenty-four rats were lightly anesthetized with halothane and maintained spontaneous breathing. UHS was induced by blood withdrawal of 2.5 ml/100 g over 15 min, followed by 75% tail amputation. Immediately after the tail cut, the rats were randomly divided into three groups (eight rats for each); normothermic Group 1 (control, rectal temperature 38 degrees C), and mild hypothermic Groups 2 (36 degrees C) and 3 (34 degrees C). Hypothermia was induced and maintained by body surface cooling. The rats were then observed without fluid resuscitation until their death (apnea and no pulse) or for a period of 240 min maximum. RESULTS The rectal temperature was cooled down to 36 and 34 degrees C in 5 and 10 min, respectively. The mean survival time, which was 76+/-26 min in the control group (38 degrees C), was nearly doubled by mild hypothermia, 178+/-65 min for Group 2 (36 degrees C) (P<0.01 vs. control) and 144+/-54 min for Group 3 (34 degrees C) (P<0.05 vs. control) (no significant difference between Group 2 and 3). Additional blood losses from tail stumps were not significantly different among the three groups. CONCLUSION Mild hypothermia of either 36 or 34 degrees C prolongs the survival time during lethal UHS in rats.

Rapid body cooling by cold fluid infusion prolongs survival time during uncontrolled hemorrhagic shock in pigs.

OBJECTIVE The purpose of this study was to examine whether cold fluid infusion could rapidly decrease the core temperature and prolong survival during uncontrolled hemorrhagic shock in pigs. METHODS Fourteen pigs under light halothane anesthesia and spontaneous breathing underwent initial blood withdrawal of 25 mL/kg over 15 minutes, followed by uncontrolled hemorrhage (5-mm aortotomy). Immediately after the aortotomy, the pigs were randomized to receive 500 mL lactated Ringers solution at either 4 degrees C (group 1, n = 7) or 37 degrees C (group 2, n = 7) over 20 minutes through the internal jugular vein and observed until their death or for a maximum of 240 minutes. RESULTS The pulmonary artery temperature of group 1 decreased to 35.5 degrees +/- 0.3 degrees C after the infusion, then remained at 35.5 degrees C during the observation period. Pulmonary artery temperature values of group 2 remained at around 37.5 degrees C throughout the experiment. The mean survival time was 220 +/- 45 minutes in group 1 versus 136 +/- 64 minutes in group 2 (p < 0.05, life table analysis). The additional intraperitoneal blood loss of group 1 was similar to that of group 2 (9 +/- 4 g/kg vs. 10 +/- 5 g/kg). CONCLUSION In lightly anesthetized pigs during uncontrolled hemorrhagic shock, infusion with 4 degrees C lactated Ringers solution (which seems to be feasible in the clinical setting) decreases the core temperature rapidly and prolongs survival.

An arteriovenous fistula between the internal mammary artery and the pulmonary vein following blunt chest trauma.

A 67-year-old man suffered a traffic accident and was transferred to an emergency hospital close to the scene. He was diagnosed to have bilateral pneumohemothorax with a lung contusion, an anterior fracture dislocation of the C6-vertebra and a cervical cord injury at the level of C7. On the 48th day, massive hemoptysis was suddenly recognized. He was transferred in a state of shock to our hospital to undergo hemostasis for the bleeding. On the day of admission, a selective arteriogram showed extravasation from the left bronchial artery, for which embolization was carried out using Gelfoam. In spite of this treatment, his hemoptysis continued. On the next day, a selective left internal mammary arteriogram showed an arteriovenous fistula between the left internal mammary artery and the left pulmonary vein without any apparent extravasation. The arteriovenous fistula was successfully embolized using platinum fiber coils. The patient no longer demonstrated any hemoptysis after embolization.

Serum interleukin-8 as a predictive marker for a comparative neurologic outcome analysis of patients resuscitated after cardiopulmonary arrest.

To the Editor: As pointed out by Dr. Marion and colleagues (1) in their recent article in Critical Care Medicine and Drs. Zornow and Prough (2) in their accompanying editorial, the definitive test of the utility of an intervention is its impact on clinical outcome. Unfortunately, for many situations in the intensive care unit such data do not exist and we must rely on intermediate physiologic outcome measures. Dr. Marion and colleagues’ article was one such study; the authors used in vivo brain microdialysis to study the brief episodes of hyperventilation (HV) in patients with traumatic brain injury (TBI). When an intermediate indirect outcome measure is used, the choice of the appropriate physiologic variable is critical. The choice should be based on our best understanding of the normal physiology of the organ, the pathophysiologic process involved, and the physiologic impact of the intervention under study. Early investigations of severe TBI patients used intracranial pressure (ICP) and later cerebral blood flow (CBF) as the physiologic end points. Since CBF was found to be low shortly after TBI and since HV reduces CBF, it became irrefutable dogma that TBI was associated with ischemia and that HV could exacerbate the situation. This conclusion may have been premature. ICP and CBF are physiologic measures that, outside of extreme conditions, are indirectly and remotely related to outcome in TBI. In normal individuals, HV lowers CBF, increases oxygen extraction, and elevates jugular venous lactate concentrations (3). Thus, ICP and CBF may not be the best end points. This point was emphasized in the accompanying editorial, which states, “Diagnosis of ischemia requires some evidence that cerebral oxygen delivery has decreased below the level necessary to maintain cerebral homeostasis.” Dr. Marion and colleagues chose an outcome measure that is closer to a direct assessment of cerebral function: in vivo microdialysis. The “minor” increases in glutamate and lactate, as they were called in the editorial, are probably within the range of normal values. Similar increases in lactate concentration with HV have been reported to occur in humans without a change in high-energy phosphate concentrations. The lactate/ pyruvate ratio, which is considered a better index of ischemia, increased slightly, but only during the initial HV trial. Yet, both the authors and editorialists concluded that aggressive HV should be avoided because of the risk of ischemia. Were this the extent of our knowledge, their conclusion could be warranted. However, they fail to consider recent direct measurements of regional cerebral metabolic rate of oxygen (CMRO2) using positron emission tomography. Those studies unequivocally found that HV, to the same degree as used by Dr. Marion and colleagues, did not result in a decrease in CMRO2 in any brain region, even in areas where CBF fell to 10 mL·100 g ·min 1 during HV (4). CMRO2 is a direct measure of brain function and thus more closely approximates neurologic function than do extracellular concentrations of intermediate metabolites. Therefore, basing their recommendations for the use of HV in TBI on minor changes in metabolites and ignoring direct measures of metabolism seem unwarranted. This concern is compounded when in an earlier report on microdialysis in TBI patients, the same group concluded that “there was no evidence of ischemia” (5). There is growing evidence that TBI is associated with suppressed metabolism rather than ischemia. Thus, low CBF is a consequence rather than a cause of reduced metabolism. Our positron emission tomography studies found low CMRO2 and reduced oxygen extraction in acute TBI patients (6). Similar findings have been reported for intracerebral hemorrhage and subarachnoid hemorrhage. Biopsies from TBI patients have indicated that suppressed mitochondrial function may be responsible for the low metabolism. Thus, the role of ischemia in TBI remains elusive at best or more likely unimportant. The best physiologic data to date indicate that brief transient HV does not cause ischemia, and recommendations should take that into consideration.