Roger E. Hofer

Temperature Changes of greater or equal to 1 degree Celsius Alter Functional Neurologic Outcome and Histopathology in a Canine Model of Complete Cerebral Ischemia

Background Changes in basal temperature of greater or equal to 1 degree Celsius (e.g., fever-induced hyperthermia or anesthesia-related hypothermia) are a common occurrence in neurologically impaired patients. The current study tested the hypothesis that temperature changes as small as 1 degree Celsius or 2 degrees Celsius would significantly alter post-ischemic functional neurologic outcome and cerebral histopathology. The hypothesis was tested in a canine model of transient, complete cerebral ischemia.

Anesthesia for a patient with morbid obesity using dexmedetomidine without narcotics

PurposeTo describe the anesthetic management of a patient with extreme obesity undergoing bariatric surgery whose intraoperative narcotic management was entirely substituted with dexmedetomidine.Clinical featuresWe describe a 433-kg morbidly obese patient with obstructive sleep apnea and pulmonary hypertension who underwent Roux-en-Y gastric bypass. Because of the concern that the use of narcotics might cause postoperative respiratory depression, we substituted their intraoperative use with a continuous infusion of dexmedetomidine (0.7µg·kg-1·hr-1). The anesthesia course was uneventful, and the intraoperative use of dexmedetomidine was associated with low anesthetic requirements (0.5 minimum alveolar concentration). After completion of the operation and after tracheal extubation, the dexmedetomidine infusion was continued uninterrupted throughout the end of the first postoperative day. The analgesic effects of dexmedetomidine extended narcotic-sparing effects into the postoperative period; the patient had lower narcotic requirements during the first postoperative day [48 mg of morphine by patient-controlled analgesia (PCA)] while still receiving dexmedetomidine, compared to the second postoperative day (morphine 148 mg by PCA) with similar pain scores.ConclusionDexmedetomidine may be a useful anesthetic adjunct for patients who are susceptible to narcotic-induced respiratory depression. In this morbidly obese patient the narcotic-sparing effects of dexmedetomidine were evident both intraoperatively and postoperatively.RésuméObjectifDécrire la démarche anesthésique utilisée chez un patient atteint d’obésité morbide devant subir un pontage gastrique. Les narcotiques peropératoires ont été entièrement remplacés par la dexmédétomidine.Éléments cliniquesLe patient pesait 433 kg, présentait une apnée du sommeil obstructive et de l’hypertension pulmonaire. Il devait subir un pontage gastrique de Roux-en-Y. Inquiets de causer une dépression respiratoire postopératoire en utilisant des narcotiques, nous avons substitué leur usage peropératoire par une perfusion continue de dexmédétomidine (0,7 µg·kg-1·hr-1). L’anesthésie s’est bien déroulée et l’usage peropératoire de dexmédétomidine a été associé à de faibles demandes d’anesthésiques (concentration alvéolaire minimale de 0,5). Après l’opération et l’extubation endotrachéale, la perfusion continue de dexmédétomidine a été poursuivie jusqu’à la fin du premier jour postopératoire. La dexmédétomidine a permis d’économiser aussi les narcotiques après l’opération; le patient a demandé moins de narcotiques pendant le premier jour postopératoire [48 mg de morphine en analgésie autocontrôlée (AAC)] tout en recevant la dexmédétomidine, comparativement au deuxième jour (148 mg de morphine en AAC). Les scores de douleur étaient comparables.ConclusionLa dexmédétomidine peut être un ajout anesthésique utile chez les patients susceptibles de dépression respiratoire induite par les narcotiques. Les effets d’économie de narcotiques de la dexmédétomidine ont été évidents ici pendant et après l’opération.

Obesity as a Risk Factor for Unanticipated Admissions After Ambulatory Surgery

OBJECTIVE To test the hypothesis that obesity is an independent risk factor for unplanned hospital admission or readmission among patients scheduled for ambulatory surgery in a tertiary medical center. PATIENTS AND METHODS Existing databases were used to identify 235 obese patients (body mass index [BMI] >40) scheduled for ambulatory surgery from January 2, 2002, through December 31, 2003, at Mayo Clinics site in Rochester, MN. Each patient was matched to a normal-weight control (BMI <25) by age, sex, surgical procedure, type of anesthesia, and date of surgery, and the medical records of all patients were reviewed. Conditional logistic regression analysis was performed to assess whether obesity is an independent risk factor for unplanned postoperative hospital admission. In all cases, 2-sided tests were performed. P<.05 was considered statistically significant. RESULTS Obese patients (mean +/- SD BMI, 44+/-4) were matched with control patients (mean +/- SD BMI, 23+/-2). Comorbidity was more frequent in the obese cohort. The frequency of unplanned hospital admission did not differ between groups: 61 obese patients (26.0%) and 52 control patients (22.1%) were admitted (odds ratio, 1.3; 95% confidence interval, 0.8-2.0; P=.30). CONCLUSION Obesity is not a significant independent risk factor for unplanned admission after ambulatory surgery, suggesting that obesity per se should not prevent ambulatory surgery from being scheduled.

Intrathecal anesthesia and recovery from radical prostatectomy: a prospective, randomized, controlled trial.

BackgroundPrevious studies suggest that intraoperative anesthetic care may influence postoperative pain and recovery from surgery. The authors tested the hypothesis that the addition of intrathecal analgesia to general anesthesia would improve long-term functional status and decrease pain in patients undergoing radical retropubic prostatectomy. MethodsOne hundred patients received either general anesthesia supplemented with intravenous fentanyl or general anesthesia preceded by intrathecal administration of bupivacaine (15 mg), clonidine (75 &mgr;g), and morphine (0.2 mg). Patients and providers were masked to treatment assignment. All patients received multimodal pain management postoperatively. Primary outcomes included pain and functional status over the first 12 postoperative weeks. ResultsPatients receiving intrathecal analgesia required more intravenous fluids and vasopressors intraoperatively. Pain was well controlled throughout the study (mean numerical pain scores < 3 in both groups at all times studied). Intrathecal analgesia decreased pain and supplemental intravenous morphine use over the first postoperative day but increased the frequency of pruritus. Pain and functional status after discharge from the hospital did not differ between groups. Intrathecal analgesia significantly decreased the duration of hospital stay (from 2.8 ± 2.0 to 2.1 ± 0.5 days; P < 0.01) as a result of five patients in the control group who stayed in the hospital more than 3 days. ConclusionsThe benefits of improved immediate analgesia and decreased morphine requirements resulting from intrathecal analgesia must be weighed against factors such as pruritus, increased intraoperative requirement for fluids and vasopressors, and resources needed to implement this modality. Further studies are needed to determine the significance of the decrease in duration of hospital stay.

Metabolism of Glucose, Glycogen, and High-energy Phosphates during Transient Forebrain Ischemia in Diabetic Rats: Effect of Insulin Treatment

Background Hyperglycemia associated with diabetes mellitus will exacerbate neurologic injury after global brain ischemia. Studies in a rat model of forebrain ischemia (bilateral carotid occlusion plus hypotension for 10 min) discovered that acute restoration of normoglycemia in diabetics, using an insulin infusion, resulted in a neurologic outcome that was similar to normoglycemic rats without diabetes. The current study evaluated cerebral glucose, glycogen, lactate, and high-energy phosphate concentrations to identify metabolic correlates that might account for an alteration in postischemic outcome. Methods Fifty-four pentobarbital-anesthetized Sprague-Dawley rats were assigned to three groups: chronically hyperglycemic diabetic rats (D; N = 18); insulin-treated, acutely normoglycemic diabetic rats (ID; N = 18); and nondiabetic rats (ND; N = 18). These groups were further divided into groups of six rats each that received either no ischemia, forebrain ischemia of 10 min duration without reperfusion, or ischemia plus 15 min of reperfusion. Brains were excised after in situ freezing, and metabolites were measured using enzymatic fluorometric techniques. Results Before ischemia, D rats had greater concentrations of brain glucose (12.18+/-2.67 micro mol/g) than did either ID (5.10 +/-1.33) or ND (3.20+/-0.27) rats (P < 0.05). Preischemic brain glycogen was similar in all groups. At the completion of ischemia, brain lactate concentrations in D were 86% greater than in ID and 61% greater than in ND (P < 0.05), reflecting a higher intraischemic consumption of glucose plus glycogen in D (P < 0.05). High-energy phosphate concentrations, as assessed by the energy charge of the adenylate pool, were better preserved in D (energy charge = 0.60 +/-0.28) than in either ID (0.29+/-0.09) or ND (0.36 +/-0.07; P < 0.05) rats. After 15 min of reperfusion, the energy charge returned to preischemic values (i.e., 0.91-0.92) in all groups. Conclusions These studies demonstrated greater intraischemic carbohydrate consumption and lactate production in D than in ID or ND rats. Under these conditions, intraischemic--but not postischemic-energy status was better in D rats. Acute insulin therapy in ID rats resulted in a metabolic profile that was similar to that of ND rats. These results suggest that, in this model, primary energy failure during ischemia is not the origin of greater injury in hyperglycemic diabetics, nor is energy enhancement the origin of improved outcome after acute insulin treatment.

Norepinephrine Does Not Potentiate Porcine Malignant Hyperthermia

Malignant hyperthermia (MH) is a rare genetic trait characterized by potential life-threatening episodes of hypermetabolism, hyperthermia, and muscle rigidity when susceptible humans or animals are exposed to triggering drugs. The role of norepinephrine (NE) in triggering MH is controversial. The purpose of this study was to show that NE does not initiate nor speed the onset of MH in susceptible swine exposed to known triggering drugs. Three groups of MH susceptible (MHS) pigs were exposed to two times the minimum alveolar anesthetic concentration (MAC) halothane (2%) for 60 min and monitored continuously until a PaCO2 of 70 mm Hg was obtained as an end point for fulminant MH. This dose of halothane is associated with significant hypotension which was addressed by three modalities: no treatment; NE infusion at 8 micro gram centered dot kg-1 centered dot min-1; and intraaortic balloon pump (IABP) with 1:1 augmentation (7.0-mL balloon catheter). NE and epinephrine (Epi) plasma levels were determined at 15-min intervals and at trigger time. All animals developed signs of MH during the study. There was no difference in pHa, lactate, PaCO (2), or temperature at control or trigger times between groups. Time to trigger was longer in the untreated group compared to both the NE and the IABP groups which were equal. The NE group had greater NE and Epi plasma levels at all times than either the untreated or IABP group and the levels increased at each sample time. The IABP group had increased NE levels at time of trigger compared to control time period, however, Epi levels did not increase. In the untreated group, individual animals had marked increases in NE levels, but extreme variability in response prevented achievement of a significant mean change. This group showed no increase in plasma Epi levels throughout the study. There was no difference in NE levels between the untreated and IABP groups. Three animals in the untreated group died prior to trigger due to complications of hypotension. In conclusion, addition of exogenous NE in high doses did not enhance triggering of MH. The large dose NE infusion resulted in increased total catecholamines throughout the study in the NE group with no effect on time to MH trigger compared to animals where mean arterial pressure (MAP) was maintained by IABP. Animals in all three groups with times to trigger of less than 30 min had significantly higher MAPs at control, 15 min, and trigger time than those with times to trigger of greater than 30 min. We conclude that NE does not trigger MH and that severe reduction of MAP delays the onset of MH in susceptible swine. (Anesth Analg 1996;82:790-5)

The Effect of a Platelet Activating Factor Antagonist (BN 52021) on Neurologic Outcome and Histopathology in a Canine Model of Complete Cerebral Ischemia

Background:Research has demonstrated that platelet activating factor may modulate, in part, the severity of postischemic neurologic injury. The proposed mechanism involves a platelet activating factor-mediated release of cerebral cellular lipids and free fatty acids, resulting in increased cerebral edema and cell injury. The present study tested the hypothesis that a specific platelet activating factor antagonist, BN 52021, would improve neurologic outcome after 12 min of complete global cerebral ischemia in a canine model. Methods:Using an established canine model of complete cerebral ischemia, dogs were assigned randomly to receive, in a blinded fashion, either 20 mg/kg BN 52021 intravenously (N = 8) or placebo (N = 7) 5 min before cerebral ischemia. After cerebral ischemia and recovery, neurologic assessment was performed by a blinded observer for 72 h. Immediately thereafter, the brains were harvested and later were evaluated histologically by a neuropathologist blinded to the treatment groups. Results:Dogs were well matched for systemic physiologic variables during all portions of the study. One placebo-treated dog and one BN 52021-treated dog were not included in the statistical analysis because of failure to meet preestablished protocol criteria. BN 52021, when compared to placebo, affected neither neurologic functional recovery nor overall histopathology scores. Regional histopathology was improved in BN 52021-treated dogs in only 1 of 18 brain regions studied (i.e., the parietal cortex). When both treatment groups were combined, there was a significant correlation between neurologic function rank and histopathology rank. Conclusions:The present data demonstrate that the platelet activating factor antagonist BN 52021, at a dose of 20 mg/kg intravenously given 5 min before cerebral ischemia, did not protect the brain from injury in this canine model of complete global ischemia.

Effect of hydroxyethyl starch solutions on blood glucose concentrations in diabetic and nondiabetic rats

Background and MethodsThe effects of iv infusions of 6% hetastarch or 10% pentastarch on blood glucose concentrations were tested in 12 nondiabetic and 12 streptozotocin-induced diabetic pentobarbital-anesthetized Sprague-Dawley rats weighing 313 to 473 g. All rats were paralyzed and mechanically ventilated. After control measurements of blood glucose concentrations were taken, rats were divided into four groups. Groups 1 (n = 6) and 2 (n = 6) comprised nondiabetic rats that received iv infusions of hetastarch or pentastarch, respectively, at a rate of 2.0 mL over 30 mins. Groups 3 (n = 6) and 4 (n = 6) comprised diabetic rats that also received iv hetastarch or pentastarch, respectively, at the same rate and duration of infusion. ResultsNeither hetastarch nor pentastarch infusions significantly altered blood glucose values over the 3-hr study period, regardless of whether the rats were diabetic or nondiabetic. ConclusionsAssuming these data are transferable to humans, the authors conclude that hydroxyethyl starch solutions do not produce or exacerbate hyperglycemia, and furthermore, that their use is not contraindicated in subjects having hyperglycemia from diabetes mellitus or iatrogenic causes.

The effects of continuous glucose infusion on blood, plasma, and brain glucose in anesthetized rats

In models of cerebral ischemia, it is important to rigidly control brain glucose in the peri-ischemic period because alterations in brain glucose can affect the severity of the postischemic injury. The following study evaluated the effect of a continuous glucose infusion as a means of producing stable increases in brain glucose that could be monitored by measuring either blood or plasma glucose. Fifty-four halothane-anesthetized rats were studied. Rats received either no treatment (control group; N = 6), saline 2 ml/h (N = 24), or glucose 1 g/kg per h in saline 2 ml/h (N = 24). In the latter two groups, samples of blood, plasma, and brain glucose were obtained at either 30, 60, 120, or 180 min of the infusion (N = 6 per group per sample period). Saline infusion had no effect on either blood, plasma, or brain glucose. In contrast, glucose infusion produced a significant increase in all three variables, achieving plateau increases during the 60-180 min measurement periods [blood glucose = 197 +/- 20 mg/dl (mean +/- S.D.) at 60 min, 220 +/- 34 mg/dl at 120 min, and 217 +/- 22 mg/dl at 180 min versus control blood glucose = 89 +/- 10 mg/dl]. Regardless of the treatment group, there was excellent correlation between blood and plasma glucose (r = 0.99; P much less than 0.001), blood and brain glucose (r = 0.96; P much less than 0.001), and plasma and brain glucose (r = 0.97; P much less than 0.001). The authors conclude that continuous glucose infusions are an effective method to produce stable increases in brain glucose in experimental models; and, in contrast to other methods for achieving brain glucose increases, the brain glucose increases can be accurately assessed by measuring blood or plasma glucose.

Fructose-1,6-bisphosphate and fructose-2,6-bisphosphate do not influence brain carbohydrate or high-energy phosphate metabolism in a rat model of forebrain ischemia

Phosphorylated fructose compounds have been reported to lessen neuronal injury in in vitro models of hypoxia and in vivo models of ischemia. Although a variety of mechanisms have been proposed to account for this finding, it is unknown if intracellular uptake and incorporation of these compounds into the glycolytic pathway contribute to the benefit. We evaluated phosphorylated fructose administration in an adult rat model of transient, near-complete cerebral ischemia to determine its impact on brain metabolism before, during, and after ischemia. Fifty-four pentobarbital anesthetized rats were randomly assigned to receive IV infusions of either fructose-1,6-bisphosphate, fructose-2,6-bisphosphate, or 0.9% saline. After 2 hours of infusion, 18 rats (6/treatment group) were subjected to brain harvesting before any ischemia, 18 additional rats had brain harvesting at the completion of 10 minutes of forebrain ischemia (2-vessel occlusion plus induced hypotension), and 18 rats had harvesting after ischemia and 15 minutes of reperfusion. Cortical brain samples were analyzed for ATP, ADP, AMP, phosphocreatine, glucose, and glycogen. When compared with placebo, neither phosphorylated fructose compound altered preischemic, intraischemic, or postischemic concentrations of brain high-energy phosphates, glucose, glycogen, or lactate, nor did they influence the intraischemic metabolism of endogenous brain glucose or glycogen. On the basis of these results, we conclude that mechanisms other than augmented carbohydrate metabolism are responsible for previous reports of neuronal protection by the bisphosphonates.