Harvey M. Shapiro

The effect of ethnicity on prescriptions for patient-controlled analgesia for post-operative pain

&NA; We studied if ethnicity influences patient‐controlled analgesia (PCA) for the treatment of post‐operative pain. Using a retrospective record review, we examined data from all patients treated with PCA for post‐operative pain from January to June 1993. We excluded patients who did not have surgery prior to the prescription of PCA or were not prescribed PCA in the immediate post‐operative period. The sample consisted of 454 subjects. While there were no differences in the amount of narcotic self‐administered, there were significant differences in the amount of narcotic prescribed among Asians, Blacks, Hispanics, and Whites (F = 7.352, P < 0.01). The ethnic differences in prescribed analgesic persisted after controlling for age, gender, pre‐operative use of narcotics, pain site, and insurance status. Patients ethnicity has a greater impact on the amount of narcotic prescribed by the physician than on the amount of narcotic self‐administered by the patient.

MK-801, an Excitatory Amino Acid Antagonist, Does Not Improve Neurologic Outcome Following Cardiac Arrest in Cats

The excitatory amino antagonist MK-801 was administered to cats following resuscitation from cardiac arrest to evaluate its effect on neurologic and neuropathology outcome in a clinically relevant model of complete cerebral ischemia. In 29 cats studied, cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was successfully performed in 21 cats. Four animals underwent a sham arrest. MK-801 or placebo was administered in a blinded, randomized manner. Beginning at 5 min post resuscitation (PR), MK-801 330 μg/kg over 2 min followed by 73 μg/kg/h for 10 h or the same volume of placebo was administered. Resuscitated animals remained paralyzed and sedated in an intensive care setting for 24–30 h PR. Neurologic examinations were performed at 2, 4, and 7 days PR by observers blinded to the treatment groups. Seventeen cats were entered into data analysis (nine MK-801-treated and eight placebo-treated). MK-801-treated animals had a significantly greater neurologic deficit score (NDS) rank (0 = normal, 100 = brain death) 2 days PR (mean rank 12.1 vs. 5.6; p = 0.008). This difference is most likely due to ongoing sedative actions of MK-801. There were no significant differences in NDS rank at 4 (10.3, MK-801 vs. 7.5, placebo) and 7 (9.6, MK-801 vs. 8.3, placebo) days PR. There were no significant differences in frontal cortex, hippocampus, occipital cortex, or cerebellar neuropathology between groups. Sham-arrested cats had normal neurologic and neuropathologic evaluations. In the circumstance of complete cerebral ischemia as employed in the current study, MK-801 had no beneficial effect upon neurologic or neuropathologic outcome.

Glucose administration before cardiac arrest worsens neurologic outcome in cats.

The effects of glucose on neurologic and neuropathologic outcome following global cerebral ischemia were examined in 20 cats subjected to 14 min of cardiac arrest, followed by closed chest resuscitation and intensive care monitoring. Beginning 30 min prior to cardiac arrest, 15 ml/kg of 5% dextrose in 0.45% saline or the same volume of 0.9% saline was administered in a blinded fashion over 15 min. Ventricular fibrillation was electrically induced and cardiac resuscitation was performed according to a standardized protocol, which included closed chest cardiac compressions, epinephrine, lidocaine, sodium bicarbonate administration, and electrical defibrillation. Animals not resuscitated within 4 min were excluded from further study. Resuscitated animals were managed in an intensive care setting for 24 h postresuscitation. Neurologic deficits were scored at 2, 4, and 7 days postresuscitation. Subsequently, the animals brains underwent histologic examination. Nine cats were excluded from data analysis. Three did not meet protocol criteria and six could not be resuscitated within 4 min. As a result of a technical error, the brain of one glucose-treated cat was not analyzed. Six saline-treated and five glucose-treated animals met all protocol criteria and survived for 7 days postresuscitation. Plasma glucose concentration before cardiac arrest was 118 +/- 24 mg/dl (mean +/- SD) in the saline group and 269 +/- 21 mg/dl in the glucose group (P less than 0.01). Neurologic outcome rank at 2, 4, and 7 days postresuscitation was significantly worse in glucose-treated cats (P less than 0.01, P less than 0.01, and P less than 0.01, respectively). The neuropathologic score did not differ between glucose- and saline-treated groups (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain surface protrusion during enflurane, halothane, and isoflurane anesthesia in cats.

Using a noncontact displacement transducer, the authors measured protrusion of the feline cortical surface through a standardized craniotomy during acute equi-MAC exposures to enflurane, halothane, and isoflurane. Each agent was studied at 0.5, 1.0, and 1.5 MAC concentrations (plus 75% N2O) without support of blood pressure. A repeat 1.0 MAC exposure was made, during which angiotensin was infused to maintain mean arterial pressure (BP) at approximately 145 mmHg. Normocapnia was maintained during all studies. In the absence of BP support, halothane produced significantly greater protrusion of the brain surface than did equi-MAC concentrations of isoflurane at all levels and greater protrusion than enflurane at 1.0 and 1.5 MAC. Halothane-induced protrusion exceeded that seen during isoflurane administration by a factor of 2.5 at 0.5 MAC (P The results indicate that enflurane (1.0 and 1.5 MAC) and isoflurane (all levels) cause markedly less protrusion of the brain into a craniotomy than does halothane. The findings roughly parallel the known effects of these agents on cerebral blood flow and probably reflect differences in anesthetic-induced changes in cerebral blood volume. If applicable to human anesthesia, they suggest that in situations during intracranial surgery where administration of a volatile anesthetic is deemed preferable to the use of an additional fixed agent, that isoflurane may be the volatile agent of choice.

Nimodipine does not improve neurologic outcome after 14 minutes of cardiac arrest in cats.

We tested the effects of nimodipine upon neurologic outcome in 31 cats subjected to 14 minutes of cardiac arrest followed by resuscitation. With the dose schedule used, nimodipine had no effect upon neurologic outcome or upon the percentage of ischemic neurons in frontal, hippocampal, occipital, or cerebellar brain sections. The electroencephalographic recovery pattern did not correlate with neurologic or pathologic findings.

Local cerebral metabolism during enflurane anesthesia: Identification of epileptogenic foci

Electrocorticographic (ECoG) and depth recordings have previously demonstrated the epileptogenic nature of surgical concentrations of the volatile anesthetic enflurane. We contrasted ECoG activity with local cerebral glucose uptake [( 14C]2-deoxyglucose autoradiography) in 23 brain structures in order to identify the epileptogenic foci. Autoradiograms were obtained from sectioned rat brain following a 30 min period of steady-state anesthesia at 1, 1.5, or 2 MAC (minimum alveolar concentration) enflurane. Pseudo-epileptiform ECoGs were obtained at 1 MAC where bursts of slow waves and sharp waves were evoked by peripheral sensory stimulation. At 1.5 MAC, the ECoG displayed frank, spontaneous epileptiform activity with large amplitude spike-wave complexes; repetitive auditory stimulation occasionally precipitated grand-mal seizures. At 2 MAC, spike complexes were less frequent and could not be repetitively driven. At 1 MAC enflurane, regional cerebral metabolism was generally depressed approximately 14% from the awake controls. However, metabolism in the dentate gyrus of the hippocampus and other subcortical structures in the limbic brain was increased. At 1.5 MAC this dichotomy in local cerebral metabolic rate was maximal; we observed increased metabolism in the hippocampus, habenula, habenulo-interpeduncular tract and interpeduncular nucleus and pineal. Metabolism in all other structures was significantly depressed (P less than 0.05) compared to awake values. At 2 MAC, metabolism was decreased in all structures. We conclude that the low seizure threshold hippocampus and related structures associated with the limbic system and its pathways are the epileptogenic foci for seizures induced with enflurane in the rat. At 1.5 MAC, epileptiform activity spreads throughout the visceral brain when seizure threshold is at a minimum.

The influence of diurnal rhythms in patients with intracranial hypertension: implications for management.

Decompensation of brain injured patients during the night is common and has been attributed to the retention of CO2 during sleep. When CO2 is controlled, such nocturnal decompensation needs another explanation; consequently, the records of 21 consecutive patients with acute closed head injuries and increased intracranial pressure were reviewed. There were 185 separate episodes of intracranial hypertension (30 mm Hg or more for 10 minutes or more) in the 21 patients, 124 of which (67%) occurred between 4:00 a.m. and 9:00 a.m. (p less than 0.01). Intravenous pentobarbital (3 to 5 mg/kg) was effective in reducing the intracranial pressure (ICP) to normal levels during 104 of the 124 early morning episodes (84%), whereas mannitol was less effective (7 of 17; 41%). This suggests that an increase in brain blood volume directly related to diurnal rhythm is responsible for the increase in ICP. Severe bradycardia and systemic arterial hypertension were unreliable predictors of elevation in ICP. They preceded or accompanied less than one-fourth of the episodes.

Nitrous oxide withdrawal reduces intracranial pressure in the presence of pneumocephalus

Nitrous oxide anesthesia has been implicated as contributing to the development of delayed tension pneumocephalus following surgery performed in the sitting position. The authors tested the hypothesis that withdrawal of nitrous oxide anesthesia administered during formation of an intracranial gas cavity would lead to a decrease in intracranial pressure (ICP) as N2O diffuses from the cavity back into the blood. Ten halothane-anesthetized rabbits were prepared for measurement of supracortical ICP and arterial blood pressure (BP) and for intracranial volume alterations via a cisterna magna infusion catheter. Hyperventilation (Paco2 = 28–30 mmHg) and mannitol were used to shrink the brain to accommodate intracranial infusion of either air or lactated Ringers (LR) solution, which was used to elevate ICP to between 10–15 mmHg from a baseline ICP of 2.1 ± 2.5 mmHg over a period of 8 to 10 min. Following stabilization at an elevated ICP, inhalation of nitrous oxide (75%) was either initiated or withdrawn (if already present during the induced ICP increase) and the subsequent changes in mean ICP and BP were recorded. Following ICP elevation with LR to 10 ± 1 mmHg, initiation of 75% N2O administration resulted in no change in ICP and modest increases (P< 0.05) in BP and cerebral perfusion pressure (CPP = BP -ICP) after 4 min. However, when ICP was raised (to 12 ± 3.5 mmHg) with intracranial air infusion, subsequent initiation of 75% N2O inhalation caused an abrupt ICP increase to 22.3 ± 9 mmHg (from control P < 0.001). Withdrawal of N2O after ICP had been elevated (15.2 ± 1.0 mmHg) by air infusion during N2O administration caused an abrupt and significant (P < 0.001) decrease in ICP ranging to 5.0 ± 4.6 mmHg, accompanied by a modest BP decline. These results confirm that N2O can diffuse back into the blood stream from a previously equilibrated intracranial gas cavity and lowers ICP when N2O is eliminated from the inspired gases. These findings suggest that discontinuance of N2O anesthesia after cranial-dural closure in patients who have a potential for developing significant pneumocephalus might reduce the potential for development of delayed tension pneumocephalus following craniectomy performed in the sitting position.

Local cerebral blood flow with fentanyl-induced seizures.

Local cerebral blood flow (LCBF) was evaluated with the [14C]iodoantipyrine quantitative autoradiographic technique in 29 brain structures in conscious control rats and during fentanyl-induced electroencephalographic (EEG) spike and/or seizure activity and in the postseizure EEG suppression phase. During spike activity, LCBF increased in all structures; the increase reached statistical significance (p < 0.05) in the superior colliculus, sensorimotor cortex, and pineal body (+ 130%, + 187%, and + 185% from control, respectively). With progressive development of seizure activity, LCBF significantly increased in 24 brain structures (range, +58% to +231% from control). During the postseizure EEG suppression phase, LCBF remained elevated in all structures (+80% to +390% from control). The local cerebrovascular resistance (LCVR) significantly decreased in 10 of 29 structures with the onset of spike activity (range, –24% to –64%), and remained decreased in all brain structures during seizure activity (range, –34% to –67%) and during the EEG suppression phase (range, –24% to –74%). This reduction of LCVR represents a near maximal state of cerebrovasodilation during fentanyl-induced EEG seizure or postseizure suppression activity. The global nature of the LCBF elevation indicates that factors other than local metabolic control are responsible for CBF regulation during local seizure activity.

Effects of levemopamil on neurologic and histologic outcome after cardiac arrest in cats.

Background and MethodsA study was performed to examine the effects of the calcium-channel blocker levemopamil on neurologic outcome and neuropathology in a clinically relevant model of complete global cerebral ischemia (ventricular fibrillation in cats). Levemopamil was administered to cats starting 5 mins after resuscitation from 14 mins of cardiac arrest. In a “blinded” manner, 46 animals received levemopamil 1 mg/kg over 15 mins followed by 10 μg/kg-min for 16 hrs or vehicle. In a nonblinded manner, eight additional animals were pretreated with levemopamil beginning 45 mins before cardiac arrest. After resuscitation, levemopamil was infused at 10 μg/kg·min for 16 hrs. Animals in all three groups remained sedated, paralyzed, and mechanically ventilated for 24 to 30 hrs after resuscitation. Neurologic examinations were performed at 2, 4, and 7 days after resuscitation. Thirty-five cats were entered into data analysis (16 levemopamil posttreated, 14 vehicle-treated, and 5 levemopamil pretreated). ResultsNeurologic deficit scores and over-all neuropathologic scores did not differ among groups at any interval after resuscitation. However, the occipital cortex and CAl region of the pretreated animals showed less severe damage than was observed in the animals that received levemopamil or vehicle, starting after resuscitation (p < .01). ConclusionsPostarrest administration of levemopamil was not associated with improved neurologic or neuropathologic outcome. However, the data suggest that prearrest administration may result in regionally selective improvement in neuropathology. (Crit Care Med 1992; 20:126)