RESUMEN
BACKGROUND: Recent studies have challenged current guidelines for prehospital fluid resuscitation. However, long-term studies evaluating the consequences of fluid restriction in uncontrolled hemorrhagic shock are lacking. This study was done to examine the long-term effects of deliberate hypotension in the treatment of uncontrolled hemorrhage. STUDY DESIGN: Uncontrolled hemorrhagic shock was produced in 40 rats by a preliminary bleed (3 mL per 100 g) followed by 75 percent tail amputation. Experimental design consisted of three phases: a "prehospital phase" (90 minutes of uncontrolled bleeding with or without treatment with lactated Ringer's [LR] solution), followed by a "hospital phase" (60 minutes, including control of hemorrhage and fluid resuscitation including blood), and a three day observation phase. Forty rats were studied in four treatment groups (ten rats per group). Group 1 consisted of untreated controls (no resuscitation). Group 2 had no fluid during the prehospital phase. Group 3 had prehospital resuscitation to a mean arterial pressure (MAP) of 40 mm Hg with LR, and group 4 had prehospital resuscitation to MAP of 80 mm Hg with LR. Groups 2, 3, and 4 received fluid and blood to MAP of 80 mm Hg and hematocrit of 30 percent in the hospital phase. RESULTS: All rats in group 1 (untreated) died within 2.5 hours. Five rats in group 2 (no prehospital FR) survived 90 minutes; however, only one survived three days. In group 3, all ten rats survived 2.5 hours and six survived three days. In group 4, eight rats died within 90 minutes, but none survived long-term. Blood loss (mL per 100 g) for each group was 3.75 0.6 for group 1, 3.35 0.1 for group 2, 4.15 0.8 for group 3, and 8.45 0.6 for group 4, (p < 0.05, group 4 compared with groups 1, 2, and 3). CONCLUSIONS: Attempts to achieve normal MAP during uncontrolled bleeding increased blood loss, hemodilution and mortality. Hypotensive resuscitation resulted in less acidemia and improved long-term survival.
Asunto(s)
Fluidoterapia/métodos , Choque Hemorrágico/terapia , Animales , Presión Sanguínea , Transfusión Sanguínea , Hospitalización , Hipotensión/fisiopatología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Usually sporadic, pheochromocytoma can, on occasion, complicate genetic disorders, such as neurofibromatosis 1, von Hippel-Lindau disease, and multiple endocrine neoplasia 2; some families seem to have just pheochromocytoma, where it may have occurred by chance. The natural history of a large kindred believed to have an excess of pheochromocytoma 34 years ago was followed with the hypothesis that the predisposition was, in fact, present and that family education and surveillance would decrease mortality. METHODS: Prospective observation and diagnostic surveillance for pheochromocytoma were conducted on the inception cohort, defined as three branches of the kindred in 1960. Of 619 descendants of three (of 11) siblings of German origin, 333 were evaluated in person at least once in the three decades of surveillance. No pheochromocytomas were known to have occurred in the eight other branches. A total of 522 persons from the 11 branches were evaluated. RESULTS: Five of the eight initial patients with pheochromocytoma died of cardiovascular complications attributable to the tumor. In follow-up, eight additional relatives were newly diagnosed with pheochromocytomas (at an average age of 19 years), and others had additional or recurrent pheochromocytomas, meningioma, para-adrenal paraganglioma, and a functioning glomus vagale; none died. CONCLUSIONS: A continuing excess of pheochromocytoma seems present in the family. Whether the incompletely penetrant gene in this family is allelic to the von Hippel-Lindau gene on chromosome 3 or is a distinct locus remains to be resolved with molecular studies. Meanwhile, education and surveillance seem to decrease mortality from pheochromocytoma in this family.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Alelos , Feocromocitoma/genética , Enfermedad de von Hippel-Lindau/genética , Adolescente , Neoplasias de las Glándulas Suprarrenales/complicaciones , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Feocromocitoma/complicaciones , Estudios Prospectivos , Enfermedad de von Hippel-Lindau/complicacionesRESUMEN
OBJECTIVE: Previously, we documented that mild hypothermia (34 degrees C) induced immediately with reperfusion after ventricular fibrillation cardiac arrest in dogs improves functional and morphologic cerebral outcome. This study was designed to test the hypothesis that a 15-min delay in the initiation of cooling after reperfusion would offset this beneficial effect. DESIGN: Prospective, randomized, controlled study. SETTING: Animal intensive care unit. SUBJECTS: A total of 22 custom-bred coonhounds. INTERVENTIONS: Eighteen dogs underwent normothermic ventricular fibrillation arrest (no blood flow) of 12.5 mins, reperfusion with brief cardiopulmonary bypass, defibrillation within 5 mins, intermittent positive-pressure ventilation to 20 hrs, and intensive care to 96 hrs. Three groups of six dogs each were studied: group 1, normothermic controls; group 2, core temperature 34 degrees C from reperfusion to 1 hr; and group 3, delayed initiation of cooling until 15 mins after normothermic reperfusion, and 34 degrees C from 15 mins to 1 hr 15 mins after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Tympanic membrane temperature (which represented brain temperature) in group 2 reached 34 degrees C at 6 +/- 3 (SD) mins after reperfusion; and in group 3 at 29 +/- 1 mins after reperfusion. Best overall performance categories achieved (1, normal; 5, brain death) compared with group 1, were better in group 2 (p < 0.5) but not in group 3 (NS). Similar results were found with best neurologic deficit scores (0%, normal; 100%, brain death), i.e., 44 +/- 4% in group 1, 19 +/- 15% in group 2 (p < .01), and 38 +/- 9% in group 3 (NS). Total brain histologic damage scores (< 30 minimal damage; > 100 severe damage), however, were 150 +/- 32 in group 1, 81 +/- 13 in group 2 (p < .001 vs. group 1), and 107 +/- 17 in group 3 (p < .05 vs. group 1). CONCLUSIONS: Mild, resuscitative cerebral hypothermia induced immediately with reperfusion after cardiac arrest improves cerebral functional and morphologic outcome, whereas a delay of 15 mins in initiation of cooling after reperfusion may not improve functional outcome, although it may slightly decrease tissue damage.
Asunto(s)
Daño Encefálico Crónico/etiología , Paro Cardíaco/terapia , Hipotermia Inducida/métodos , Resucitación/métodos , Fibrilación Ventricular/complicaciones , Animales , Análisis de los Gases de la Sangre , Glucemia/análisis , Temperatura Corporal , Daño Encefálico Crónico/clasificación , Daño Encefálico Crónico/patología , Puente Cardiopulmonar , Cuidados Críticos , Modelos Animales de Enfermedad , Perros , Cardioversión Eléctrica , Paro Cardíaco/sangre , Paro Cardíaco/complicaciones , Paro Cardíaco/fisiopatología , Hematócrito , Ventilación con Presión Positiva Intermitente , Masculino , Pronóstico , Distribución Aleatoria , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Fibrilación Ventricular/terapiaRESUMEN
Since 1970 we have investigated postischemic anoxic encephalopathy and potential treatments for cerebral resuscitation after cardiac arrest by cardiopulmonary-cerebral resuscitation (CPCR). The post-resuscitation syndrome has been studied at the levels of cell, organ, organism and community. Short-term and long-term models in rats, dogs, and monkeys have been developed, and an international multicenter randomized clinical trial mechanism was established. Clinical studies disproved the 5-min limit of reversible cardiac arrest and yielded other valuable data on treatments and prognostication. Thiopental loading or calcium entry blocker therapy (lidoflazine) gave no significant improvement in patients. Free radical scavengers are under investigation in the laboratory. We hypothesize that post-arrest perfusion failure and necrotizing cascades require etiology-specific combination treatments. Standard (control) therapy in a current dog model of cardiac arrest (no flow) of 12.5-20 min, reperfusion with cardiopulmonary bypass, and intensive care for 72-96 h has consistently resulted in survival with brain damage. After ventricular-fibrillation (VF) arrest of 17 min, moderate hypothermia (28-32 degrees C) inconsistently improved cerebral outcome. After VF arrest of 12.5 min, hypertension plus hemodilution normalized the local (multifocal) cerebral hypoperfusion post-arrest and, again, inconsistently improved cerebral outcome. Additional mild hypothermia (34-36 degrees C), however, consistently improved cerebral outcome, whether induced before or during and after arrest.
Asunto(s)
Presión Sanguínea/fisiología , Daño Encefálico Crónico/fisiopatología , Puente Cardiopulmonar , Paro Cardíaco/fisiopatología , Hemodilución , Hipotermia Inducida , Hipoxia Encefálica/fisiopatología , Resucitación , Animales , Encéfalo/irrigación sanguínea , Encéfalo/patología , Encéfalo/fisiopatología , Daño Encefálico Crónico/patología , Perros , Metabolismo Energético/fisiología , Haplorrinos , Paro Cardíaco/patología , Hipoxia Encefálica/patología , Presión Intracraneal/fisiología , Ratas , Flujo Sanguíneo Regional/fisiologíaRESUMEN
BACKGROUND AND PURPOSE: Mild cerebral hypothermia (34 degrees C) induced immediately after cardiac arrest improves outcome. Deep postarrest hypothermia (15 degrees C) has not been studied. METHODS: We used our dog model of normothermic ventricular fibrillation (no blood flow) of 12.5 minutes, reperfusion by brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 72 hours. Head surface cooling and bypass cooling were performed from start of reperfusion to 1 hour. Five groups of six dogs each were compared: group I, normothermic controls; group II, deep hypothermia (15 degrees C); group III, moderate hypothermia (30 degrees C); group IV, mild hypothermia (34 degrees C); and group V, mild hypothermia with head surface cooling begun during no flow. RESULTS: In control group I, five dogs remained comatose (overall performance category [OPC] 4) and one severely disabled (OPC 3). In group II, four dogs achieved OPC 4 and two dogs OPC 3 (NS versus group I). Compared with group I, OPCs were better in group III (p less than 0.05), group IV (p less than 0.05), and group V (p less than 0.05). Neurological deficit scores were also better in groups III, IV, and V than in groups I or II (p less than 0.05). Total brain histological damage scores were better in group III (p = 0.02), group IV (p = 0.06), and group V (p less than 0.05) than in group I. In group II, OPC and neurological deficit scores were the same and histological damage scores numerically worse than in group I and all were worse than in groups III, IV, and V (p less than 0.05). Cardiovascular complications and myocardial morphological damage in groups II and III were worse than in groups I, IV, and V (p less than 0.05). CONCLUSIONS: Mild or moderate cerebral hypothermia induced immediately after cardiac arrest improves cerebral outcome, more likely when initiated during arrest, whereas deep postarrest hypothermia can worsen cerebral and cardiac outcome.
Asunto(s)
Paro Cardíaco/terapia , Hipotermia Inducida/métodos , Daño por Reperfusión/prevención & control , Resucitación/métodos , Animales , Encéfalo/patología , Modelos Animales de Enfermedad , Perros , Paro Cardíaco/patología , Miocardio/patologíaRESUMEN
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.