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.

Painless electrodiagnostic current perception threshold and pain tolerance threshold values in CRPS subjects and healthy controls: a multicenter study.

The purpose of this study is to evaluate both painless and painful sensory transmission in patients with Complex Regional Pain Syndrome (CRPS) using the automated electrodiagnostic sensory Nerve Conduction Threshold (sNCT) test. This test generates reliable, painless Current Perception Threshold (CPT) and atraumatic Pain Tolerance Threshold (PTT) measures. Standardized CPT and PTT measures using constant alternating current sinusoid waveform stimulus at 3 different frequencies 5 Hz, 250 Hz, and 2 kHz (Neurometer CPT/C Neurotron, Inc. Baltimore, MD) were obtained from CRPS subjects at a distal phalange of the affected extremity and at an ipsilateral asymptomatic control site. Matched sites were tested on healthy subjects. Detection sensitivities for an abnormal PTT and CPT test were calculated based on specificity of 90% as determined from data obtained from healthy controls. A Spearman rank correlation was used to test for a significant association between presence of allodynia and an abnormal PTT or CPT at any frequency tested. Thirty-six CRPS subjects and 57 healthy controls were tested. The highest detection sensitivity of the PTT test from symptomatic test sites was 63% for the finger and 71% for the toe. PTT abnormalities were also detected, to a lesser degree, at the asymptomatic control site (41% finger control site, 16% toe control site). The highest CPT detection sensitivity at the symptomatic site was 37% for the finger site and 53% for the toe site. CPT abnormalities were also detected at the asymptomatic control site (29% finger control site, 37% toe control site). Eighty-six percent of the CRPS subjects had either a PTT or CPT abnormality at any frequency at the symptomatic site. There was a significant correlation between presence of allodynia and presence of an abnormal CPT and PTT, respectively (P < .01). The correlation coefficient was lower for CPT than for PTT, ie, 0.34 versus 0.6 for the finger and 0.48 versus 0.67 for the toe, respectively. In studied CRPS patients an abnormal PTT was detected with higher sensitivity than an abnormal CPT. Assessing PTT may become a useful electrodiagnostic quantitative sensory test for diagnosing and following the course of neuropathic pain conditions.

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.

Evolution of epidural lysis of adhesions.

Epidural neuroplasty (lysis of epidural adhesions) is an interventional technique that has emerged over the last 10 years as part of a multidisciplinary approach to treating radiculopathy with low back pain when conservative management has failed. Neuroplasty was at one time performed as a single-catheter technique using the caudal approach. It now has many variations, including placement of the catheter tip in the anterior epidural space. This article will discuss the evolution and refinement of epidural neuroplasty at our institution.

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.

Time lines and computer-based visual editing: new techniques for assessing exposure in epidemiologic studies.

We describe a time-line-based methodology for collecting exposure data for epidemiologic studies and for processing these data for statistical analysis with readily available software for the personal computer. The four components to this approach are: (1) collecting data in a memory-enhancing time-line format; (2) entering data from time lines into a computer database and editing them; (3) making a quantitative estimate of exposure, intake, or dose for each exposure event; and (4) creating analysis datasets by 'slicing' the quantified time lines based on desired exposure intervals or disease latent periods. Compared with fixed-format interviews, time-line-based interviews help subjects organize remembered events, thereby reducing confusion. They do not restrict responses to predetermined categorical exposure responses. The time-line methodology also facilitates the collection of supplementary data necessary for computing doses for complex exposures and the packaging of quantified exposures into analysis datasets for any time period of interest.

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.

The Development of a Technique for Radiofrequency Lesioning of Splanchnic Nerves.

This article describes the development of a technique for radiofrequency lesioning of the splanchnic nerves. It features point neurolysis and improvement in safety from previously described techniques with the use of a curved, blunt needle. After extensive anatomic studies, the site of entry has been identified 4 cm lateral to the spinous process at the costovertebral angle of either the T11 or T12 vertebral body, and the placement of the needle tip at the junction of posterior two thirds to the anterior one third of the vertebral body. The use of a sharp, straight needle has been discouraged to prevent pneumothorax, and bowel, kidney, or nerve root injury. The radiofrequency lesion permits a point neurolysis, thus decreasing the rate of complications. Our experience of 22 patients treated with this technique has been complication-free, and the outcome was effective for all 10 patients with cancer. In the nonmalignancy group, some patients needed a second neurolysis (radiofrequency) procedure 4 months apart. There were also no secondary complications in these patients. We expect multicenter data accumulation in the coming years, which will determine the true efficacy of the radiofrequency of splanchnic nerves.

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.