Search PubMed⌕ Search

Biomedical subjects

P Safar

Publications and source records attributed to P Safar.

At least 145 records · Page 8Linked to original sources
PubMed1990

Evaporative cooling as an adjunct to ice bag use after resuscitation from heat-induced arrest in a primate model.

Heat stroke and other hyperthermia-related crises are serious clinical problems in childhood and adolescence. Rapid cooling is required to reduce morbidity and mortality. A variety of effective cooling methods exist, and some may interfere with monitoring and resuscitation or are not readily available. We studied in 12 pigtail monkeys the pathophysiology of immersion hyperthermia (42 degrees C) to cardiac arrest (1 min no flow) and CPR plus cooling to normothermia for restoration and stabilization of spontaneous normotension. This was followed by intractable shock and secondary arrest. These studies gave us the opportunity to compare two simple cooling methods applied during and after CPR: group I (n = 6) received application of ice bags to the groins, axillae, and neck. Group II (n = 6) received ice bags plus cold water wetting (sponging) over the entire anterior surface of trunk and extremities, plus fanning. CPR restored spontaneous circulation in four of six in each group, after CPR of 1.5-16 min (NS between groups). Speed of cooling correlated with speed of stabilization of spontaneous normotension. After cardiac arrest and during and after CPR, rectal temperature had declined from a lethal level of 42.2 degrees C to a safe level of 38.5 degrees C within 45 +/- 6 (38-53) min in group I, and within 28 +/- 4 (23-32) min in group II (p less than 0.05). Epidural and esophageal temperatures declined more rapidly than rectal temperature. For critical hyperthermia, we recommend immediate application of ice bags, cold water wetting (sponging), fanning, and head cooling combined when invasive blood cooling (the most effective method) is not immediately available.

Animals↗
PubMed1990

Therapeutic deep hypothermic circulatory arrest in dogs: a resuscitation modality for hemorrhagic shock with 'irreparable' injury.

Early deaths from trauma are often caused by exsanguinating hemorrhage from injuries that appear "irreparable." We explored the limits of deep hypothermic circulatory arrest induced during hemorrhagic shock to enable repair of these injuries in a bloodless field. In 15 dogs, after 30 minutes of hemorrhagic shock (mean arterial pressure, 40 mm Hg), cardiopulmonary bypass (CPB) was used to cool to 15 degrees C in 13-37 minutes. After circulatory arrest of 60 (Group 1), 90 (Group 2), or 120 (Group 3) minutes, reperfusion and rewarming were accomplished by CPB. All dogs survived greater than 72 hours. Best neurologic deficit scores (ND) (0% = normal, 100% = brain death) were 0 +/- 0% (normal) in Group 1, 10 +/- 8% (mild disability) in Group 2, and 27 +/- 24% in Group 3. Outcome in Group 3 dogs ranged from near-normal to comatose. After perfusion-fixation sacrifice, brain histopathologic damage scores correlated with insult time, as did ND scores. Deep hypothermia can allow 60-90 min of circulatory arrest with good neurologic recovery, even after a period of severe hemorrhagic shock. This technique may allow repair of otherwise lethal injuries and survival without brain damage.

Animals↗
PubMed1989

The physician's responsibility toward hopelessly ill patients. A second look.

Physicians have a specific responsibility toward patients who are hopelessly ill, dying, or in the end stages of an incurable disease. In a summary of current practices affecting the care of dying patients, we give particular emphasis to changes that have become commonplace since the early 1980s. Implementation of accepted policies has been deficient in certain areas, including the initiation of timely discussions with patients about dying, the solicitation and execution in advance of their directives for terminal care, the education of medical students and residents, and the formulation of institutional guidelines. The appropriate and, if necessary, aggressive use of pain-relieving substances is recommended, even when such use may result in shortened life. We emphasize the value of a sensitive approach to care--one that is adjusted continually to suit the changing needs of the patient as death approaches. Possible settings for death are reviewed, including the home, the hospital, the intensive care unit, and the nursing home. Finally, we consider the physician's response to the dying patient who is rational and desires suicide or euthanasia.

Ethics, Medical↗
PubMed1989

Effect of cardiac arrest time on cortical cerebral blood flow during subsequent standard external cardiopulmonary resuscitation in rabbits.

Standard external cardiopulmonary resuscitation (SECPR) produces high cerebral venous and intracranial pressure peaks, low cerebral perfusion pressure, and low cerebral blood flow (CBF). Cerebral viability seems to require 20% of normal CBF, which SECPR cannot reliably generate. We tested the hypothesis that SECPR can produce adequate CBF if started immediately, but not if started after a long period of cardiac arrest (no flow, stasis). Cardiac arrest times of 1, 3, 5, 7 and 9 min were studied in rabbits. We measured unifocal cortical CBF with H2 clearance curves after saturation with H2 10%, O2 50% and N2O 40% by intermittent positive-pressure ventilation (IPPV). Measurements were made during spontaneous circulation (control condition), and then after resaturation immediately before induction of asystole by KCl i.v., and H2 clearance starting at end of arrest time during SECPR-basic life support with IPPV 100% and manual chest compressions (120/min) during asystole. Control cortical CBF was 30-40 ml/100 g brain per min. During asystole and SECPR, CBF greater than 20% normal was achieved only after no-flow of 1 min. After longer arrest (no-flow) times, CBF was less than 20% normal. Values were near zero after 7 and 9 min of cardiac arrest. Decrease in mean arterial pressures (MAP) produced by SECPR during asystole paralleled CBF values. Thus, the longer the preceding period of stasis, the lower the MAP and CBF generated by SECPR without epinephrine. This effect may be the result of anoxia-induced vasoparalysis and stasis-induced increased blood viscosity.

Animals↗
PubMed1989

New monkey model of severe-volume controlled hemorrhagic shock.

Three series of experiments were conducted to develop a model of volume-controlled severe hemorrhagic shock in the unanesthetized analgesic cynomolgus monkey. This report concerns the insult without resuscitation. In Series I, seven monkeys were sedated with 75% N2O/25% O2, bled 40% of their measured blood volume over 20 min and observed until death. Mean arterial pressure (MAP) decreased to 21 +/- 6 mmHg, spontaneously increased to 46 +/- 5 mmHg, then gradually decreased to pulselessness at 146 +/- 42 min (range 101-213). Hemodynamic variables, lactate, base excess, electroencephalogram and sagittal sinus PO2 followed the same biphasic pattern. In Series II, eight monkeys were bled 27 ml/kg (43% of estimated blood volume) over 20 min under the same N2O analgesia and with similar responses as in Series I. In Series III 26 monkeys were bled 27 ml/kg over 20 min (time zero) as in Series II. Three developed apnea and pulselessness at end of hemorrhage. In 23 the shock period was prolonged for testing resuscitation therapies. Starting at 0 + 30 min, MAP was controlled with minute blood volume adjustments at 30 mmHg until 0 + 2 h. Three died due to inaccurate (preventable) MAP adjustments. At MAP 30 mmHg, all animals lost consciousness, EEG activity decreased, and brain stem reflexes disappeared. The "volume-pressure controlled" hemorrhagic shock model of Series III retains the initial natural response to bleeding, simulates the clinical picture of severe prolonged shock without anesthesia, and represents a more controllable insult than volume controlled hemorrhage alone.

Animals↗
PubMed1989

Brain enzyme changes as markers of brain damage in rat cardiac arrest model. Effects of corticosteroid therapy.

Apneic asphyxia to cardiac arrest (CA) in rats of 10 min was reversed by cardiopulmonary resuscitation (CPR), and after controlled ventilation and controlled normotension for 20 min, was followed by decapitation and brain freezing, and determination of brain concentrations of cytosolic and lysosomal enzymes. Normal values came from a control group of 10 rats without CA. In 20 rats with CA brain cytosolic enzymes CK, LD, and ASAT decreased post-arrest, while lysosomal enzyme changes were variable (Table I). Brain lactate increased 8-10-fold post-CA. To test the model, effect of methylprednisolone (MP) was studied. The 20 rats with CA were divided into 4 groups: Group I, received placebo pre-CA; Group II, MP 30 mg/kg i.v. pre-CA; Group III, placebo post-CA; and Group IV, MP post-CA. The post-CA MP Group IV was the only one without norepinephrine requirement and with return of EEG activity at 20 min. Brain CK, LD, and ASAT losses post-CA were not different between groups; and showed no differences between MP groups II and IV vs. placebo Groups I and III. When comparing both pre-CA Groups (I and II) with both post-CA Groups (III and IV), post-CA CK and ASAT levels were the same, but LD was higher in the post-CA treatment group. The lysosomal enzymes acid phosphatase, mannosidase, beta-glucuronidase and hexosaminidase showed variable concentration changes post-CA in the four groups, with a trend toward a lesser increase of some after MP or after post-treatment. Brain enzyme changes in our asphyxial CA rat model can serve as markers of brain damage. MP post-CA might enhance cardiovascular and EEG recovery, but does not seem to influence brain enzyme levels at 20 min post-CA.

Animals↗
PubMed1989

Initiation of closed-chest cardiopulmonary resuscitation basic life support. A personal history.

Modern external (closed-chest) cardiopulmonary resuscitation (CPR) basic life support (BLS) gives everyone anywhere a chance to initiate the reversal of death from airway obstruction, apnea, or pulselessness. The history of modern CPR has its roots around 1900, but lay dormant for half a century, until in the 1950s several fortunate circumstances merged to allow for documentation of Steps A (airway control by head-tilt and jaw-thrust), B (breathing control by mouth-to-mouth ventilation), and C (circulation control by closed-chest cardiac massage, i.e. chest compressions) and their combination into BLS Steps A-B-C. BLS is only for borderline emergency oxygenation, i.e. Phase I of the life support chain. Both the non-authoritarian environment of the U.S.A. and several role players with keen interest in resuscitation were needed to enable the systematic research (Steps A and B), a chance rediscovery (Step C), and the integration of BLS with advanced life support (ALS, drugs and defibrillation, transferred from open-chest CPR) and brain-oriented prolonged life support (PLS, intensive care) to result in the development of an effective cardiopulmonary-cerebral resuscitation system. A fertile environment led rapidly to the development of resuscitation delivery systems in hospitals and communities. This paper is a story told by one of the role players.

History, 20th Century↗
PubMed1989

Effect of excitatory amino acid receptor blocker MK-801 on overall, neurologic, and morphologic outcome after prolonged cardiac arrest in dogs.

Excitatory amino acids accumulating in the brain during ischemia may cause selective neuronal damage postischemia. This hypothesis was tested in a series of studies using MK-801, an N-methyl-D-aspartate (NMDA) receptor blocker, in a reproducible outcome model of prolonged cardiac arrest in dogs. After normothermic ventricular fibrillation cardiac arrest, the dogs were resuscitated with closed-chest femoral veno-arterial cardiopulmonary bypass. At 4 h they were separated from bypass, ventilation was controlled for 20 h, and intensive care was continued to 96 h. In Study I, ventricular fibrilation cardiac arrest (no-flow) was 17 min; starting immediately with reperfusion, MK-801 1200 mg/kg (n = 5) or an equal volume of placebo (n = 5) was infused over 12 h in blinded, randomized fashion. In Study II, the duration of the no-flow period was reduced to 15 min, and MK-801 2400 mg.kg-1 (n = 4) or placebo (n = 4) was infused. In Study III, no-flow lasted for 15 min, and MK-801 2400 mg/kg was started 30 min before ventricular fibrillation (n = 4); comparison was with Study II controls. In all three studies, MK-801 plasma concentrations peaked at greater than 50 ng/ml and were 15-30 ng/ml over 12 h. All 22 dogs of experiments within protocol survived with severe brain damage. MK-801 delayed return of pupillary reactivity, EEG activity, consciousness, and respiration, necessitating longer periods of controlled ventilation. Neurologic deficit scores, overall performance categories, and brain and heart morphologic damage scores at 96 h did not differ between placebo and MK-801 pretreatment or post-treatment groups. These negative outcome results after prolonged cardiac arrest do not negate the hyperexcitability hypothesis of selective vulnerability, but suggest the existance of additional mechanisms of secondary brain damage.

Animals↗
PubMed1989

The presenting ECG pattern in survivors of cardiac arrest and its relation to the subsequent long-term survival. Brain Resuscitation Clinical Trial I Study Group.

In a prospective multi-center study, 262 patients were given general intensive care therapy following cardiopulmonary resuscitation if they were still comatose and unresponsive to pain 10 min after restored spontaneous circulation. Mortality (mainly cardiac) was 53.4% over the first 10 days, and 49% of the remaining survivors died between 10 days and 6 months. In the subsequent 6 months few patients died. Presenting electrocardiograms (ECG) showed ventricular fibrillation (VF) in 54.2%, asystole in 29.8% and electromechanical dissociation (EMD) in 9.2% of the patients. One-year survival, 14.1% for asystole, 4.2% for EMD and 26.0% for VF and VT (ventricular tachycardia), differed significantly (P less than 0.01). VF/VT patients were older and had more cardiovascular disease. Adjustments of these and other covariates increased the significance of difference between ECG groups. Successful resuscitations from asystole or EMD appeared to be more common than has previously been reported, but this group of patients experienced an extremely high cardiac mortality over the first 6 months following resuscitation.

Electrocardiography↗
PubMed1988

Predictors of electromechanical dissociation during cardiac arrest.

ECG patterns observed during cardiac arrest were analyzed in 261 comatose cardiac arrest survivors. Forty-seven patients (18%) exhibited electromechanical dissociation (EMD) at some point before restoration of stable spontaneous circulation. These patients had a higher mortality (P = .05) and a lower rate of cerebral recovery (P = .01) during the one-year follow-up than study patients who did not exhibit EMD. Patients who developed EMD subsequent to defibrillation had better outcome than patients presenting with EMD. Multivariate analysis revealed that age more than 70 years old (P = .007), pulmonary disease (P less than .001), diabetes (P = .013, in-hospital arrests only), and prearrest hypoxemia (P = .013, outside-hospital arrests only) were independently predictive of the occurrence of EMD. Although the generalizability of these findings is limited, they may offer new clues to the pathophysiology of EMD.

Aged↗
PubMed1988

Brain enzyme levels in CSF after cardiac arrest and resuscitation in dogs: markers of damage and predictors of outcome.

Levels of brain creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD) in CSF after cardiac arrest were studied in dog models. Ventricular fibrillation cardiac arrest lasting 10 min or asphyxiation cardiac arrest lasting 0-10 min was followed by cardiopulmonary resuscitation and 96-h intensive care. Outcome was scored as neurologic deficit (0% = normal, 100% = brain death) and overall performance category (1 = normal, 5 = death). Both measures correlated with EEG return time after asphyxiation cardiac arrest, but not after ventricular fibrillation cardiac arrest. Peak activity of enzymes in CSF at 48-72 h post arrest correlated with outcome, and CK was the best predictor. Brain histopathologic damage score at autopsy 96 h post arrest correlated with CK level in CSF (r = 0.79, n = 39) and neurologic deficit (r = 0.70, n = 50). Ischemic neuronal changes occurred after ventricular fibrillation cardiac arrest of 10 min, and neuronal changes plus microinfarcts occurred after asphyxiation cardiac arrest of 1.5-10 min. Brain enzymes were decreased at 6 h post arrest in regions with worst histologic damage (gray matter of neocortex, hippocampus, caudate nucleus, cerebellum). Brain CK decreased further, ASAT remained low, and LD increased at 72 h after arrest. The temporal changes in CK level paralleled the temporal ischemic neuronal changes in the brain, and time to peak activity was unaffected by the severity of the ischemic insult. Peak activity of individual enzymes in CSF was determined predominantly by the brain concentration, but was also influenced by rate of decomposition. This "chemical brain biopsy method" represents a useful adjunctive tool to predict permanent, severe brain damage during comatose states after cardiac arrest and resuscitation.

Animals↗
PubMed1988

Resuscitation from clinical death: pathophysiologic limits and therapeutic potentials.

Modern cardiopulmonary-cerebral resuscitation (CPCR) for the reversal of clinical death (i.e., prolonged cardiac arrest) is a sequence of basic, advanced and prolonged life-support steps. This system was initiated by research that started in the 1950s. Present community-wide results are encouraging, but suboptimal. Maximal benefit from CPCR will be achievable: a) by minimizing response times; and b) by extending reversible arrest times--the topic of this symposium. For reperfusion, closed chest CPR is more readily available than, but physiologically inferior to, open chest CPR and emergency cardiopulmonary bypass. To optimize outcome, four components of the postresuscitation syndrome are being investigated: a) perfusion failure; b) reoxygenation injury cascades; c) self-intoxication; and d) blood derangements. Results from animal outcome studies so far suggest significant but still inconsistent benefit from several special postarrest treatments. The longest normothermic no-flow time yet reversed to good functional survival of heart, brain and the entire organism appears to be not 5 min, but between 10 and 20 min. The following is recommended and in part has been initiated: a) simultaneous investigation of pathophysiologic limits, therapeutic potentials, and prognosticating measurements; b) simultaneous basic research at cellular, organ, and organism levels; c) increased communication and consensus on research models between research centers; d) use of short-term and long-term animal models for systematic mechanism-oriented and empirical outcome-oriented studies; e) development of etiology-specific combination treatments; and f) community-wide case registries combined with epidemiologic studies and randomized clinical treatment trials.

Animals↗