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R L Lennon

Publications and source records attributed to R L Lennon.

At least 19 recordsLinked to original sources

The influence of renal function on the pharmacokinetics and pharmacodynamics and simulated time course of doxacurium.

UNLABELLED: Doxacurium's clearance (C1) is markedly decreased in patients with renal failure undergoing kidney transplantation. However, no studies have determined the influence of renal function (as assessed by creatinine clearance [CrCl]) on its pharmacokinetics in patients without renal failure. We studied 53 patients aged 19-59 yr. During N2O/isoflurane anesthesia, doxacurium was infused over 10 min, plasma was sampled for up to 6 h, and twitch tension was measured. A three-compartment model was fit to plasma concentration data and an effect compartment model to twitch data. Mixed-effects modeling was used to determine the influence of covariates, including CrC1, on doxacurium's pharmacokinetic/pharmacodynamic parameters. Obesity decreased both doxacurium's Cl (1.1% per percent above ideal body weight [IBW]) and its neuromuscular junction sensitivity (0.4% per percent above IBW). Cl increased 0.6% per mL/min increase in CrCl. In addition, the rate constant for equilibration between plasma concentration and effect decreased 46% per 1% increase in isoflurane, central compartment volume decreased 86% per 1% increase in isoflurane concentration, and slow distributional Cl decreased 69% per mg/ 100 mL increase in serum albumin. Simulations showed that the latter two covariates influence the time course of bolus doxacurium administration minimally. Both obesity and renal dysfunction prolong doxacurium's recovery markedly. When dosing is based on IBW, effects of CrCl on neuromuscular recovery are smaller compared with dosing based on actual weight. Therefore, obese patients should be dosed based on IBW. No further dosage adjustment is necessary for patients with renal dysfunction; however, recovery will take longer in patients with moderate-to-severe renal dysfunction. IMPLICATIONS: We examined the factors influencing doxacurium's pharmacokinetic and pharmacodynamic characteristics. Both creatinine clearance and obesity significantly influence its time course. The effect of obesity is minimized if patients are dosed based on ideal body weight.

Adult↗

Forearm blood flow responses to handgripping after local neuromuscular blockade.

To test the hypothesis that acetylcholine "spillover" from motor nerves contributes significantly to skeletal muscle vasodilation during exercise, we measured the forearm blood flow responses during attempted handgripping after local paralysis of the forearm with the neuromuscular-blocking drug pipecuronium. This compound blocks postsynaptic nicotinic receptors but has no impact on acetylcholine release from motor nerves. The drug was administered selectively to one forearm by using regional intravenous drug administration techniques in five subjects. Pipecuronium reduced maximum forearm grip strength from 40.0 +/- 3.2 kg before treatment to 0.0 kg after treatment. By contrast, drug administration had no effect on maximum voluntary contraction in the untreated forearm (41.3 +/- 3.3 vs. 41.4 +/- 2.7 kg). During 2 min of attempted maximal contraction of the paralyzed forearm, the forearm blood flow increased from only 3.4 +/- 0.8 to 4.8 +/- 1.2 ml.100 ml-1.min-1 (P < 0.05). Heart rate increased from 63 +/- 3 to 73 +/- 8 beats/min (P > 0.05) during attempted contraction, and only three of five subjects showed obvious increases in heart rate. Mean arterial pressure increased significantly (P < 0.05) from 102 +/- 6 to 109 +/- 9 mmHg during attempted contractions. When these increases in flow are considered in the context of the marked (10-fold or greater) increases in flow seen in contracting forearm skeletal muscle, it appears that acetylcholine spillover from motor nerves has, at most, a minimal impact on the hyperemic responses to contraction in humans.

Adult↗

Evaluation of cisatracurium, a new neuromuscular blocking agent, for tracheal intubation.

PURPOSE: The primary objective of this study was a blinded, randomized comparison of the recommended intubating dose of atracurium (0.5 mg. kg-1) with an approximately equipotent dose of cisatracurium (0.1 mg. kg-1) during N2O/O2/propofol/fentanyl anaesthesia. METHODS: Eighty ASA physical status 1 or 2 patients, 18-70 yr of age, within 30% of ideal body weight, scheduled for elective low to moderate risk surgical procedures were studied. Adductor pollicis evoked twitch responses were measured with a Grass FT 10 force displacement transducer (Grass Instruments, Quincy, MA) and continuously recorded on a Gould multichannel polygraph (Gould Instrument Systems, Cleveland, OH) after induction of anaesthesia. RESULTS: Increasing the initial dose of cisatracurium (from 0.1 to 0.15 and 0.2 mg. k-1, decreased mean time of onset (from 4.6 to 3.4 and 2.8 min, respectively), and increased mean time of clinically effective duration (45 to 55 and 61 min, respectively). Recovery to a T4:T1 ratio of 0.7 occurred approximately seven minutes following administration of the reversal agent neostigmine for all treatment groups. Intubation conditions were good or excellent in over 90% of patients in all treatment groups (two minutes after approximately 2 x ED95 doses of cisatracurium or atracurium and 1.5 minutes after 3 x and 4 x ED95 doses of cisatracurium). CONCLUSION: The intubation results reported in this study together with the combination of predictable recovery from neuromuscular block and apparent haemodynamic stability make cisatracurium a potentially useful muscle relaxant in clinical practice.

Adolescent↗

Train-of-four recovery after pharmacologic antagonism of pancuronium-, pipecuronium-, and doxacurium-induced neuromuscular block in anaesthetized humans.

Previous studies have suggested that the increased duration of action of long-acting neuromuscular relaxants may make their pharmacologic antagonism more difficult and, thus, increase the likelihood of residual block. This hypothesis was tested in healthy, adult humans who received a background of isoflurane/N2O/fentanyl anaesthesia. Study subjects were paralyzed with either pancuronium (N = 8), pipecuronium (N = 8), or the longer-acting relaxant, doxacurium (N = 8). Neuromuscular function was monitored, and, using a blinded, randomized study design, the relaxants were titrated to identify the ED95 dose in each patient. Thereafter, spontaneous recovery was observed until there was 25% of baseline response to the first supramaximal twitch (T1) in a train-of-four (TOF). At this time, the block was antagonized with neostigmine 0.07 mg/kg and glycopyrrolate 0.014 mg/kg i.v., and recovery of TOF was recorded. Spontaneous recovery to 25% of the baseline T1 response occurred at 52 +/- 14 min (mean +/- SD) following administration of either pancuronium and pipecuronium, and 85 +/- 33 min following doxacurium (P < 0.05 for doxacurium versus pancuronium and pipecuronium). In doxacurium-treated patients, reversal of block with neostigmine was less predictable and less complete than with the other two relaxants. For example, the ratio of the fourth to first twitch (T4/T1) of the TOF at 10 and 15 min after reversal was significantly less with doxacurium (59 +/- 14% and 61 +/- 16%, respectively) than with either pancuronium (75 +/- 6% and 75 +/- 10%) or pipecuronium (76 +/- 9% for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

A computer-controlled, closed-loop infusion system for infusing muscle relaxants: its use during motor-evoked potential monitoring.

A microcomputer-controlled closed-loop infusion system (MCCLIS) has been developed that provides stable intraoperative levels of partial neuromuscular blockade. Complete neuromuscular blockade interferes with intraoperative motor-evoked potential (MEP) monitoring used for patients undergoing surgical procedures that place them at risk for spinal cord ischemia. Nine patients were studied during which the MCCLIS maintained stable levels of partial neuromuscular blockade and allowed transcranial magnetic motor-evoked potential (TcM-MEP) monitoring during thoracoabdominal aortic aneurysmectomy. The use of TcM-MEP for monitoring intraoperative spinal cord function was balanced against surgical considerations for muscle relaxation with 80% to 90% neuromuscular blockade fulfilling each requirement. Intraoperative adjustment of partial neuromuscular blockade to facilitate TcM-MEP monitoring was also possible with the MCCLIS. The MCCLIS should allow for further investigation into the sensitivity, specificity, and predictability of TcM-MEP monitoring for any patient at risk for intraoperative spinal cord ischemia including those undergoing thoracoabdominal aortic aneurysmectomy.

Action Potentials↗

A versatile, computer-controlled, closed-loop system for continuous infusion of muscle relaxants.

A computer-controlled, closed-loop system for continuous infusion of muscle relaxants that allows the operator to choose either atracurium besylate or vecuronium bromide to provide any desired target level of neuromuscular blockade is described. This new system offers certain advantages over computer-controlled systems described previously for continuous infusion of muscle relaxants--that is, the option to choose either of two muscle relaxants to be infused and the inclusion of monitors to provide feedback about the dosage needed to produce a target level of neuromuscular blockade. The clinical performance of this system was tested in 36 patients who were 18 to 65 years old, were classified in American Society of Anesthesiologists physical status 1 or 2, and were undergoing elective orthopedic, abdominal, or thoracic procedures. In all patients, the control algorithm rapidly induced the target level of neuromuscular blockade and maintained that level of blockade at steady state with minimal oscillation. We conclude that the automatic feedback control system described can induce and precisely maintain any predetermined target level of neuromuscular blockade.

Adolescent↗

Cemented versus noncemented total hip arthroplasty--embolism, hemodynamics, and intrapulmonary shunting.

Bone cement implantation syndrome is characterized by hypotension, hypoxemia, cardiac arrhythmias, cardiac arrest, or any combination of these complications. It may result from venous embolization that occurs in conjunction with intramedullary hypertension in the femur during insertion of the prosthesis in patients undergoing cemented total hip arthroplasty (THA). Intramedullary hypertension does not occur in patients undergoing noncemented THA. In this study, we sought to compare embolization between patients undergoing cemented and noncemented THA and to determine whether this state resulted in cardiorespiratory deterioration. In this prospective investigation of 35 patients undergoing elective THA, we used transesophageal echocardiography and invasive hemodynamic monitoring, and in 12 of them, we monitored distribution of pulmonary ventilation and perfusion intraoperatively. Embolization was significantly greater after insertion of the prosthesis in patients undergoing cemented than in those undergoing noncemented THA. Cemented THA was also associated with decreased cardiac output and increased pulmonary artery pressure and pulmonary vascular resistance. Increases in ventilation-perfusion mismatching, however, could not be demonstrated 30 minutes after insertion of the femoral prosthesis. Intraoperative monitoring for embolism may help physicians assess patients in whom cardiorespiratory function deteriorates during THA.

Aged↗

Effect of partial neuromuscular blockade on intraoperative electromyography in patients undergoing resection of acoustic neuromas.

Intraoperative electromyographic monitoring of the facial nerve during acoustic neuroma excision provides early detection of nerve injury and improved outcome. To determine whether a useful level of peripheral neuromuscular blockade could be achieved without compromise of facial electromyographic monitoring, we studied 10 patients undergoing resection of acoustic neuroma. Facial nerve monitoring was accomplished by placement of wire electrodes in the orbicularis oris, orbicularis occuli, and mentalis muscles. Peripheral neuromuscular blockade was assessed by recording unprocessed hypothenar compound muscle action potentials (CMAPs). After induction of anesthesia, an infusion of atracurium (1.0 micrograms.kg-1.min-1) accompanied by a bolus dose of 50 micrograms/kg was administered. The infusion was then increased in increments of 0.5 micrograms.kg-1.min-1 until a 50% reduction in hypothenar single-twitch CMAP was obtained. Facial nerve function was continuously monitored by comparison of facial CMAPs produced by stimulation of the nerve proximal and distal to the tumor bed. The mean (+/- SD) infusion rate of atracurium was 2.55 +/- 0.75 micrograms.kg-1.min-1. Decrements in facial nerve CMAPs were detected in 6 of 10 patients, and all demonstrated moderate to severe facial nerve dysfunction. In no patient was an unexpected deficit present postoperatively. Moderate degrees of peripheral neuromuscular blockade can be achieved without compromising facial nerve electromyographic monitoring.

Action Potentials↗

Method of intraoperative monitoring of neuromuscular function and residual blockade in the recovery room.

We evaluated the method used intraoperatively to assess the degree of neuromuscular blockade prior to pharmacologic reversal to determine its role in preventing residual blockade in the postanesthesia care unit (PACU). We studied 38 patients who received a nondepolarizing muscle relaxant during general anesthesia for carotid endarterectomy or thoracotomy. The anesthesiologist assessed the degree of neuromuscular blockade intraoperatively prior to pharmacologic reversal either by the standard method of visually counting the number of evoked thumb twitches elicited by supramaximal train-of-four stimulation of the ulnar nerve (i.e., thumb train-of-four count), or by an alternative method such as 1) visually counting the number of evoked orbicularis oculi muscle twitches elicited by supramaximal train-of-four stimulation of the facial nerve, or 2) observing the patient for clinical evidence of partial recovery (e.g., swallowing or attempts to breathe). Residual blockade in the PACU was defined as 1) a train-of-four ratio less than 0.70 (measured by a mechanomyograph), or 2) the inability of the patient to perform clinical tests of neuromuscular function (e.g., a sustained head lift for 5 seconds) and evidence of neuromuscular weakness that was resolved following administration of edrophonium. Five of the 22 patients (23%) in whom one of the alternative methods was used had residual blockade in the PACU; none of the 16 patients with a thumb train-of-four count of 3 or 4 before pharmacologic reversal of NMB had residual blockade in the PACU (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗

Limited heat transfer between thermal compartments during rewarming in vasoconstricted patients.

Thermoregulatory vasoconstriction may serve to separate and limit heat transfer between peripheral and central thermal compartments, in effect providing a thermal buffer for central temperature. We hypothesized that thermoregulatory vasoconstriction would limit heat transfer to the central compartment in patients warmed cutaneously. Hypothermic patients (central temperatures < 35 degrees C) recovering from surgery were randomly assigned to receive forced-air warming (n = 6) or warmed cotton blankets (n = 6). The forced-air warmer delivers approximately 50 W of heat, compared to a heat loss of approximately 50 W with warmed cotton blankets. Despite a significantly greater increase in mean skin-surface temperature with forced-air warming, central temperature in the two groups did not significantly differ. All patients vasoconstricted and there was no difference in oxygen consumption between groups. These data confirm that thermoregulatory vasoconstriction limits heat transfer from peripheral to central thermal compartments and impedes skin surface warming of the body core.

Blood Pressure↗

Brachial plexus anesthesia for outpatient surgical procedures on an upper extremity.

We retrospectively reviewed 543 brachial plexus blocks performed on 526 outpatients. Most (98%) of the blocks were performed by means of the axillary approach. Various techniques were used, including paresthesia, transarterial fixation, nerve stimulation, or a combination of techniques; a high success rate was achieved with each of them. Only 7% of the blocks were incomplete and thus necessitated either general anesthesia or block supplementation with thiopental sodium and nitrous oxide. No persistent neurologic deficit was ascribed to the anesthetic technique. This review indicates that brachial plexus block, especially with use of the axillary approach, is a safe and effective option for outpatient surgical procedures on an upper extremity.

Adolescent↗

Blood flow to contracting human muscles: influence of increased sympathetic activity.

The purpose of this study was to examine the effects of the increased sympathetic activity elicited by the upright posture on blood flow to exercising human forearm muscles. Six subjects performed light and heavy rhythmic forearm exercise. Trials were conducted with the subjects supine and standing. Forearm blood flow (FBF, plethysmography) and skin blood flow (laser Doppler) were measured during brief pauses in the contractions. Arterial blood pressure and heart rate were also measured. During the first 6 min of light exercise, blood flow was similar in the supine and standing positions (approximately 15 ml.min-1.100 ml-1); from minutes 7 to 20 FBF was approximately 3-7 ml.min-1.100 ml-1 less in the standing position (P less than 0.05). When 5 min of heavy exercise immediately followed the light exercise, FBF was approximately 30-35 ml.min-1.100 ml-1 in the supine position. These values were approximately 8-12 ml.min-1.100 ml-1 greater than those observed in the upright position (P less than 0.05). When light exercise did not precede 8 min of heavy exercise, the blood flow at the end of minute 1 was similar in the supine and standing positions but was approximately 6-9 ml.min-1.100 ml-1 lower in the standing position during minutes 2-8. Heart rate was always approximately 10-20 beats higher in the upright position (P less than 0.05). Forearm skin blood flow and mean arterial pressure were similar in the two positions, indicating that the changes in FBF resulted from differences in the caliber of the resistance vessels in the forearm muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Evaluation of a forced-air system for warming hypothermic postoperative patients.

Thirty adult surgical patients admitted to the recovery room with an oral temperature less than or equal to 35.0 degrees C were randomized into two groups. Group 1 patients were covered with cotton blankets warmed to 37.0 degrees C, and group 2 patients were treated with a forced-air warming system. Mean oral temperature on admission to the recovery room was the same in both groups (34.3 degrees C). Oral temperature and the presence or absence of shivering were recorded at 15-min intervals. After application of the selected warming method, patients in group 2 were warmer at all time intervals. Mean temperatures in the forced-air heating group and in group 1 were, respectively, 34.8 degrees C and 34.3 degrees C (P less than 0.05) at 15 min; 35.0 degrees C and 34.2 degrees C (P less than 0.01) at 30 min; 35.2 degrees C and 34.5 degrees C (P less than 0.05) at 45 min; 35.8 degrees C and 34.7 degrees C (P less than 0.001) at 60 min; 36.0 degrees C and 35.0 degrees C (P less than 0.01) at 75 min; and 36.0 degrees C and 35.0 degrees C (P less than 0.01) at 90 min. The incidence of shivering was significantly greater in group 1 at 15 and 45 min. In addition, time spent in the recovery room was significantly greater in group 1 than in group 2, 156.0 min versus 99.7 min (P less than 0.003).

Adult↗

Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high dose atracurium in rabbits.

Large doses of atracurium (1.5 mg/kg) (six times the ED95) have been reported to provide adequate conditions for rapid sequence endotracheal intubation within 60 seconds in humans. However, this dose can result in significant histamine release and systemic hypotension. We therefore studied the efficacy of histamine receptor blockade in attenuating this response. Four groups of five rabbits were pretreated as follows: Group I--control, Group II--H1 blockade (1 mg/kg diphenhydramine), Group III--H2 blockade (cimetidine 4 mg/kg), and Group IV--H1 and H2 blockade (diphenhydramine 1 mg/kg and cimetidine 4 mg/kg). All rabbits were anesthetized and then 1.8 mg/kg (six times the rabbit ED95) atracurium was administered. Group I rabbits experienced a decrease in MAP of 12.2 mmHg after one minute, a change that was significantly greater than Group IV in which MAP decreased by 0.8 mmHg (p less than 0.001). H1 or H2 receptor blockade alone was associated with intermediate changes in MAP not significantly different from control. We conclude that combined H1 and H2 receptor blockade attenuates the cardiovascular effects associated with large doses of atracurium in the rabbit and that this combination of antagonist drugs might have similar effectiveness in humans.

Animals↗

Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.

The association between preoperative smoking cessation and postoperative pulmonary morbidity was studied prospectively in 200 consecutive patients undergoing an elective coronary artery bypass surgical procedure. Detailed respiratory, cardiovascular, and smoking histories were elicited. Preoperative arterial blood gas analyses and bedside spirometry were performed. Urinary cotinine levels were measured to verify smoking histories. During spirometry, severe angina developed in seven patients, who were hence excluded from the study; one patient died of hemorrhage intraoperatively. An observer unaware of patients' preoperative histories assessed the remaining 192 patients throughout the intraoperative and postoperative periods for pulmonary complications. Postoperative pulmonary complications occurred in a third of the current smokers. Patients who had stopped smoking for 2 months or less had a pulmonary complication rate almost 4 times that of patients who had stopped for more than 2 months (57.1% versus 14.5%). Patients who had stopped smoking for more than 6 months had rates similar to those who had never smoked (11.1% and 11.9%, respectively). Preoperative pulmonary dysfunction, increased pack-years of smoking, prolonged surgical time, and the use of enflurane were independently associated with postoperative pulmonary morbidity (P less than 0.05). We concluded that smoking cessation should occur at least 2 months preoperatively to maximize the reduction of postoperative respiratory complications.

Aged↗