Recovery of elderly patients from two or more hours of desflurane or sevoflurane anaesthesia.

BACKGROUND: The solubility of desflurane compared with sevoflurane suggests more rapid recovery from desflurane anaesthesia. This could be important after prolonged anaesthesia and fast recovery may be advantageous in the elderly where slow recovery of mental function is a concern. We compared emergence from desflurane vs sevoflurane in elderly patients undergoing two or more hours of anaesthesia. METHODS: Fifty ASA physical status I, II, or III patients, 65 yr of age or older, undergoing anaesthesia expected to last two or more hours were randomly assigned to receive desflurane/nitrous oxide or sevoflurane/nitrous oxide anaesthesia. Patients were given 1-2 microg x kg(-1) fentanyl i.v. and anaesthesia was induced with propofol 1.5-2.5 mg x kg(-1) i.v. and maintained with either desflurane 2-6% or sevoflurane 0.6-1.75% with nitrous oxide 65% in oxygen. Inspired anaesthetic concentrations were adjusted to obtain adequate surgical anaesthesia and to maintain mean arterial pressure within 20% of baseline values. Early and intermediate recovery times were recorded. Digit-Symbol Substitution Test (DSST) scores and Visual Analog Scale (VAS) scores for pain and nausea were recorded before pre-medication and every 15 min in the Post Anaesthesia Care Unit (PACU) until patients were discharged. RESULTS: Early recovery times are given as median, quartiles. The times to extubation (5 (4-9); 9 (5-13) min), eye opening (5 (3-5); 11 (8-16) min), squeezing fingers on command (7 (4-9); 12 (8-17) min); and orientation (7 (5-9); 16 (10-21) min) were significantly less (P<0.05) for desflurane than for sevoflurane. Intermediate recovery, as measured by the DSST and time to ready for discharge from the PACU (56 (35-81); 71 (61-81) min) was similar in the two groups. CONCLUSIONS: Early but not intermediate recovery times of elderly patients undergoing a wide range of surgical procedures requiring two or more hours of anaesthesia is significantly (P

Anesthesia update: agents, definitions, and strategies.

The trend in modern anesthesia is to "lighten up." This generally involves use of several drugs with selective and complementary actions. The pharmacokinetic properties of such drugs should allow rapid onset, rapid recovery, and rapid responses to changes in delivered doses. Peri-operative management issues also are inherent to use of modern drugs and techniques. For example, provisions must be in place for postoperative analgesia if rapid recovery is anticipated. Light anesthesia reduces morbidity and mortality, and reduces the drug, facility, and personnel costs associated with anesthesia. However, the requirements for anesthesia and the expertise of personnel administering anesthesia vary considerably. Many regulatory bodies and scientific journals require a description of how anesthesia adequacy and depth will be assessed, as well as extensive justification for the use of neuromuscular blocking agents. In environments where adequate experience and sophistication for the use of cutting edge drugs and methods are not available, older drugs and techniques may be adequate and preferable to protect animals from pain or distress.

Phenotypic expression of the systemic toxicity of cocaine in genetically epilepsy-prone rats.

The purpose of the present investigation was to determine whether the sensitivity to systemic toxic effects of cocaine is altered in genetically epilepsy-prone rats (GEPRs). Moderate seizure (GEPR-3) and severe seizure (GEPR-9) rats, and the control strain, Sprague-Dawley rats, 10 weeks of age, were lightly anesthetized with halothane and nitrous oxide. Following surgical preparation and stabilization, the animals were given a constant intravenous infusion of cocaine (4 mg/kg per min) until death. Blood pressure, ECG, and EEG were monitored continuously throughout the experiment. Cocaine doses required to produce seizures (i.e., epileptiform activity on the EEG) were not significantly different between GEPRs and control rats (16.8+/-0.6 mg/kg in GEPR-3, 18.7+/-0.7 mg/kg in GEPR-9, and 14.7+/-1.3 mg/kg in Sprague-Dawley). Seizure duration, amplitude and the number of epileptiform bursts were also similar among the three strains. Additionally, there was no significant difference in cocaine doses that produced arrhythmias and cardiac asystole between GEPRs and control. The results indicate that genetically epilepsy-prone rats do not exhibit altered sensitivity to cocaine-induced seizures despite the marked susceptibility to sound-evoked seizures. Local anesthetic-induced seizures and acoustically-evoked seizures apparently have different underlying mechanisms.

Myelinated fibers of spinal cord blood vessels--sensory innervation?

Innervation of the ventral spinal artery from the lumbosacral region of dogs was studied using light, scanning, and transmission microscopy. Microscopy revealed myelinated fibers, a new observation, in addition to unmyelinated fibers expected on the basis of previous studies of autonomic innervation of this blood vessel. The myelinated axons may be sensory fibers.

Nitric oxide modulation affects the tissue distribution and toxicity of bupivacaine.

We have previously demonstrated that inhibition of nitric oxide synthase (NOS) alters the toxicity of local anesthetics including bupivacaine. Because significant changes in blood distribution are associated with the use of nonselective NOS inhibitors, the purpose of this study was to determine whether modification of bupivacaine toxicity by nonselective NOS inhibition is due to alteration in tissue disposition of bupivacaine. Rats were anesthetized with halothane and pretreated with either: 1) a nonselective NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 2 mg/kg/min, IV for 30 min); 2) a neuronal NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg, IP); or 3) vehicle (control). Thirty minutes later, bupivacaine 2 mg/kg/min IV was infused until onset of seizures, arrhythmias, or asystole. L-NAME caused a rapid increase in plasma bupivacaine concentrations (3-4 times faster than in the other groups), which was associated with markedly lower bupivacaine doses (mg/kg) required to produce arrhythmias in L-NAME (4.2 +/- 0.5) vs. control (26 +/- 3, p < 0.01) and 7-NI groups (17 +/- 3, p < 0.01). Myocardial bupivacaine concentrations at arrhythmia onset were slightly lower in the L-NAME group. Bupivacaine seizure doses in 7-NI and L-NAME pretreated animals were similar to control but significantly different from each other. Brain bupivacaine concentrations at seizure onset were similar among the groups. There were no significant differences between 7-NI and control groups in any parameter observed. We conclude that enhanced cardiotoxicity of bupivacaine by nonselective NOS inhibition is primarily due to rapid increases in plasma and myocardial distribution of bupivacaine.

Percutaneous epidural neuroplasty: prospective evaluation of 0.9% NaCl versus 10% NaCl with or without hyaluronidase.

BACKGROUND AND OBJECTIVES: Percutaneous epidural neuroplasty (epidural neurolysis, lysis of epidural adhesions) is an interventional pain management technique that has emerged over approximately the last 10 years as part of a multidisciplinary approach to treating radiculopathy with low back pain. In addition to local anesthetic and corticosteroid, hypertonic saline (10% NaCl) and hyaluronidase are used for the technique. The objective of this study was to determine if hypertonic saline or hyaluronidase influenced treatment outcomes. METHODS: Eighty-three subjects with radiculopathy plus low back pain were assigned to one of four epidural neuroplasty treatment groups: (a) hypertonic saline plus hyaluronidase, (b) hypertonic saline, (b) isotonic saline (0.9% NaCl), or (d) isotonic saline plus hyaluronidase. Subjects in all treatment groups received epidural corticosteroid and local anesthetic. RESULTS: Twenty-four subjects did not complete the study. Most of the other 59 subjects receiving any of the four treatments as part of their pain management obtained significant relief immediately after treatment. Visual analog scale (VAS) scores for the area of maximal pain (VASmax; back or leg) were reduced in 25% or more of subjects in all treatment groups at all post-treatment follow-up times (1, 3, 6, 9, and 12 months). A smaller fraction of subjects treated with hypertonic saline or hyaluronidase and hypertonic saline required more additional treatments than did subjects receiving the other treatments. CONCLUSIONS: Percutaneous epidural neuroplasty, as part of an overall pain management strategy, reduces pain (sometimes for over one year) in 25% or more of subjects with radiculopathy plus low back pain refractory to conventional therapies. The use of hypertonic saline may reduce the number of patients that require additional treatments.

Blood pressure is maintained despite profound myocardial depression during acute bupivacaine overdose in pigs.

UNLABELLED: Bupivacaine-induced cardiovascular collapse is a feared complication because of the difficulty in restoring stable circulation (1). Early recognition is important so that the injection of bupivacaine can be discontinued. We used an animal model of near-cardiac arrest from bupivacaine infusion to identify the sequence of hemodynamic events that precedes bupivacaine-induced cardiovascular collapse. Twelve pigs (23-25 kg) were sedated with ketamine and anesthetized with halothane. Arterial blood pressure and cardiac output were measured. Bupivacaine (3.75 mg/mL) was administered at a rate of 5.73 mL/min (approximately 1 mg x kg(-1) x min(-1)) through a central venous catheter until severe ventricular arrhythmia occurred. Blood pressure and heart rate were unchanged, but cardiac output decreased by 40% with increasing doses of bupivacaine. Calculated peripheral resistance increased by 54%. The QRS complex of the surface electrocardiogram widened, and the R-wave amplitude decreased 80%, together with the decrease in cardiac output. T-wave amplitude increased initially but returned toward baseline at the largest bupivacaine doses. The plasma concentration of bupivacaine after the infusion was 16+/-6.8 microg/mL. IMPLICATIONS: The increase in vascular resistance that accompanies acute bupivacaine overdose maintains blood pressure but masks severe myocardial depression.

Nitric oxide synthesis inhibition modifies the cardiotoxicity of tetracaine and lidocaine.

UNLABELLED: Suppression of nitric oxide (NO) production alters the toxicity of cocaine and bupivacaine. We undertook this study to determine whether the systemic toxicity of two other local anesthetics that differ in antiarrhythmic activity, plasma clearance, and biotransformation are similarly affected by nitric oxide synthase (NOS) inhibition. Sprague-Dawley rats anesthetized with 70% N2O and 0.5% halothane mixed with O2 were pretreated with saline (0.2 mL x kg(-1) x min(-1) i.v.) or N(omega)-nitro-L-arginine methyl ester (L-NAME; a competitive inhibitor of NOS) (2 mg x kg(-1) x min(-1) i.v.) for 30 min. The animals were then given tetracaine (3 mg x kg(-1) x min(-1) i.v.) or lidocaine (8 mg x kg(-1) x min(-1) i.v.) until cardiac arrest (asystole). Doses of lidocaine or tetracaine that produced arrhythmias, seizures, isoelectric encephalogram, and asystole were determined. Hemodynamic recordings were performed throughout the experiments, and plasma was collected to measure the concentration of lidocaine or tetracaine. L-NAME decreased tetracaine and lidocaine doses that produced arrhythmias (> or = 2 degrees atrioventricular conduction block) (tetracaine 14 +/- 2 mg/kg; lidocaine 102 +/- 9 mg/kg) versus saline treatment (tetracaine 28 +/- 2 mg/kg; lidocaine 136 +/- 9 mg/kg; P < 0.05). The tetracaine and lidocaine doses required to produce asystole were also smaller in animals with L-NAME pretreatment than those in saline-pretreated animals. L-NAME reduced the arrhythmia dose of tetracaine more than the arrhythmia dose of lidocaine (28 of 14 = 2.0 fold and 136 of 102 = 1.3-fold). The plasma concentration of lidocaine, but not tetracaine, was significantly higher at each sample time in L-NAME-pretreated animals than in saline-pretreated animals. Inhibition of NOS by L-NAME enhances the cardiotoxicity of lidocaine and tetracaine, with a greater effect on tetracaine than on lidocaine. Altered drug clearance by L-NAME was insufficient to explain these findings because L-NAME pretreatment increased the plasma levels of only lidocaine, not tetracaine. IMPLICATIONS: Inhibition of nitric oxide production in rats markedly enhances the cardiovascular toxicity of lidocaine and tetracaine. Altered drug clearance by N(omega)-nitro-L-arginine methyl ester was insufficient to explain these findings because N(omega)-nitro-L-arginine methyl ester pretreatment increased the plasma levels of only lidocaine, not tetracaine.

Two genetically selected strains of rats exhibit hypersensitivity or resistance to cocaine-induced fatal arrhythmias.

We identified for the first time two genetically selected strains of rats that differ markedly in sensitivity to cocaine-induced life-threatening cardiac arrhythmias and arrest. The two strains of rats, designated as Fast and Slow, were bred for sensitivity (Fast) or resistance (Slow) to electrically kindled seizures. Studies were performed on halothane-anesthetized, mechanically ventilated rats. Animals were given cocaine (3 or 4 mg/kg/min i.v.) until they died. Arrhythmias (atrioventricular conduction block) developed at much lower cumulative cocaine doses in Slow-kindling rats than in Fast-kindling rats (15 +/- 1 versus 42 +/- 3 mg/kg, p <.01). The lethal cocaine dose (the dose that caused cardiac arrest) was also markedly lower in Slow than in Fast strains (32 +/- 2 versus 62 +/- 6 mg/kg, p <.01). These differences between the two strains were not significantly altered by pretreatment of animals with either ganglionic blockers, hexamethonium (20 mg/kg i.v.) or chlorisondamine (5 mg/kg i.v.), or a nonselective beta adrenergic receptor blocker, propranolol (1 mg/kg i.v.). A nonselective alpha adrenergic receptor blocker, phentolamine (10 mg/kg i.v.), however, abolished the differences between the Fast and Slow strains in the doses of cocaine required to produced atrioventricular conduction block and cardiac arrest. The results provide the first evidence of genetically determined susceptibility or resistance to cocaine-induced cardiotoxicity. There appears to be a genetically determined difference in the alpha adrenergic receptor system between the two strains that is responsible for the differential sensitivity to cocaine-induced arrhythmias and cardiac arrest.

Cocaine cardiotoxicity differs markedly in isolated hearts of two strains of rats exhibiting phenotypic differences in sensitivity to seizures.

Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vivo, differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5 x 10(-6), 1 x 10(-5), 5 x 10(-5), 1 x 10(-4), and 5 x 10(-4) M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vivo observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5 x 10(-5) M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10(-4) M cocaine. Arrest in Fast hearts occurred only with 5 x 10(-4) M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.

Thermal grill illusion and complex regional pain syndrome type I (reflex sympathetic dystrophy).

BACKGROUND AND OBJECTIVES: In normal humans, placing a hand on a thermal grill containing warm elements separated by cool ones produces a burning sensation. In this case report, responses to a thermal grill in a patient with neuropathic pain were examined. METHODS: The responses of a 31-year-old woman with complex regional pain syndrome type I (reflex sympathetic dystrophy) to a thermal grill were evaluated before and after stellate ganglion block. RESULTS: The patient experienced a burning sensation when the unaffected hand was placed on the grill and could distinguish which element was warm and which was cool. An intolerable burning sensation caused the patient to quickly (within 4 seconds) withdraw the affected hand when it was placed on the grill. Touching cool elements with the affected hand produced an intense burning sensation (cold allodynia), whereas touching warm elements produced a pleasant warm sensation. Stellate ganglion block with phenol, local anesthetic, and steroid resulted in long-lasting absence of cold allodynia. CONCLUSION: The thermal grill may be a useful a tool to help understand the pathophysiology of complex regional pain syndrome type I.

Modification of bupivacaine toxicity by nonselective versus neuronal nitric oxide synthesis inhibition.

We have previously shown that pretreatment of rats with a nonselective nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), enhances the cardiovascular system (CVS) toxicity and reduces the central nervous system (CNS) toxicity of local anesthetics. This study was performed to differentiate the neuronal from the endothelial effects of L-NAME on the CNS and CVS toxicity of bupivacaine by comparing the effects of L-NAME with a neuronal selective NOS inhibitor, 7-nitroindazole (7-NI). Lightly anesthetized rats were premedicated for 30 min with L-NAME (2 mg kg(-1) x min(-1) intravenously [I.V.]), 7-NI (30 mg/kg intraperitoneally), or saline (control) then bupivacaine (2 mg x kg(-1) x min(-1)) was infused I.V. until asystole occurred. Bupivacaine doses required to produce seizures were the same among groups (saline = 10.1 +/- 2.6 mg/kg; L-NAME = 9.0 +/- 1.2 mg/kg; 7-NI = 10.2 +/- 1.0 mg/kg). However, plasma bupivacaine concentration (microg/mL) at seizure onset was significantly higher in animals pretreated with L-NAME (16.4 +/- 2.1) and, to a lesser degree, 7-NI (11.6 +/- 1.3) than that of control (9.7 +/- 1.6). Seizure duration and the number of epileptiform bursts were significantly reduced in L-NAME versus the other two groups. Doses for arrhythmias and asystole as well as plasma bupivacaine concentrations at arrhythmia onset were dramatically smaller in L-NAME-pretreated rats than in the other two groups. In summary, endothelial NOS inhibition dramatically alters both the CVS and CNS toxicity of bupivacaine with neuronal NOS inhibition playing a minor role.

Severe dietary magnesium deficiency does not alter levels and function of myocardial Gs alpha and Gi alpha.

Magnesium ions (Mg2+) play a crucial role in the activation and synthesis of guanine nucleotide-binding proteins (G proteins). However, there is no information about the influence of in vivo magnesium deficiency on the function and levels of G proteins. This study was done to investigate whether dietary magnesium deficiency alters function and levels of the two major myocardial G proteins, Gi alpha and Gs alpha. Severe hypomagnesemia and a significant reduction of myocardial magnesium occurred in rats fed a magnesium-deficient diet for 6 wk vs. rats fed a normal-magnesium diet (control). The magnesium-deficient rats developed focal myocardial lesions but their cardiac function was not impaired. Myocardial immunodetectable Gs alpha and Gi alpha levels of magnesium-deficient rats did not differ from control (Gs alpha: 2.39 +/- 0.52 vs. 2.76 +/- 0.72 arbitrary units/microgram protein, P > 0.05; Gi alpha: 1.60 +/- 0.52 vs. 1.89 +/- 0.30 arbitrary units/microgram protein, P > 0.05). Similarly, the function of Gs alpha and Gi alpha estimated by basal and ligand-stimulated adenylyl cyclase activity was not significantly different between the two groups of animals. The results show that dietary-derived magnesium deficiency sufficient to produce severe hypomagnesemia does not produce any significant change in levels or function of myocardial G proteins.

Nitric oxide synthesis inhibition enhances bupivacaine cardiotoxicity.

BACKGROUND AND OBJECTIVES: There is evidence that local anesthetic-induced seizures may be mediated by receptors for N-methyl-D-aspartate (NMDA) which activate production of nitric oxide (NO). The objective of this study was to determine the effects, if any, of inhibition of NO synthesis on the responses of the central nervous and cardiovascular systems to bupivacaine. METHODS: Sprague-Dawley rats were assigned to two groups. The lightly anesthetized (0.5% halothane, 70% nitrous oxide) and paralyzed (doxacurium) animals were given N omega-nitro-L-arginine methyl ester (L-NAME), a NO synthase inhibitor, 2 mg/kg/min (n = 6) or saline (n = 5) intravenously for 30 minutes. Then bupivacaine was administered intravenously (2 mg/kg/min) to both groups of animals until asystole. Arterial blood samples for bupivacaine concentration analysis (by high-pressure liquid chromatography) were taken during the stabilization period and during local anesthetic infusion. Student's t-test was used to determine significant differences (P < .05) between groups. RESULTS: Average doses of bupivacaine that produced arrhythmias and asystole were remarkably lower in L-NAME-treated than in saline-treated rats (arrhythmia, 5.1 +/- 2.0 vs 15.8 +/- 3.8 mg/kg; asystole, 15.9 +/- 3.2 vs 27.8 +/- 6.1 mg/kg; both P < .05). The doses producing seizures and isoelectric electroencephalograms and the duration of seizures did not differ significantly between the two treatment groups. However, electroencephalographic epileptiform activity was less intense (lower amplitude, shorter duration of ictal activity) in the L-NAME-treated animals. Arterial plasma concentrations of bupivacaine 5 minutes after the start of bupivacaine infusion were significantly higher in the L-NAME than in the saline group (22.3 +/- 2.9 vs 12.8 +/- 1.5 micrograms/mL, P < .05). CONCLUSIONS: These results suggest that NO synthase inhibition by L-NAME enhances the cardiac toxicity of bupivacaine, probably by a pharmacokinetic action, and reduces its central nervous system toxicity, probably by a pharmacodynamic action.