Ghassem E. Larijani

Comparison of tracheal intubating conditions and neuromuscular blocking profiles after intubating doses of mivacurium chloride or succinylcholine in surgical outpatients.

Thirty ASA physical status I or II outpatients scheduled to undergo short procedures (<1 hr in duration) requiring tracheal intubation received either 1.0 mg/kg succinylcholine or 0.20 mg/kg (2.5 × ED95) or 0.25 mg/kg (3 × ED95) mivacurium. A N2O/O2/narcotic anesthetic technique was utilized and the ulnar nerve was stimulated with subcutaneous electrodes placed at the wrist. Tracheal intubation was attempted in all patients either 2 min after mivacurium or 1 min after succinylcholine. Intubation conditions were not different between the succinylcholine and mivacurium groups or between the two mivacurium groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with mivacurium. Suppression of the T1 response to 90% of baseline occurred in 0.9 min with 1.0 mg/kg succinylcholine and at 2.2 and 1.5 min respectively, with 0.20 mg/kg and 0.25 mg/kg mivacurium. Initial recovery of the T1 response occurred at 6.4 min after 1.0 mg/kg succinylcholine and 12.7 and 13.6 min respectively after 0.20 mg/kg and 0.25 mg/kg mivacurium. Subsequent to initial recovery from the intubating dose of relaxant, infusions of mivacurium or succinylcholine were administered to maintain approximately 95% block. The mean infusion rates were 6.6 μg·kg−1 ·min−1 mivacurium and 41.2 μg·kg−1 min−1 for succinylcholine. Spontaneous recovery from neuromuscular blockade occurred more quickly after succinylcholine than after mivacurium: the time from cessation of infusion to recovery of T1 to 95% of baseline was 6.5 min in patients given succinylcholine and 16.7 min in patients given mivacurium. When reversal was in order, residual mivacurium-induced blockade was readily antagonized by 0.045 mg/kg neostigmine. In a small group (n = 7) of patients given mivacurium in whom neuromuscular function was still 77–99% blocked when neostigmine was given, the average time from administration of neostigmine to recovery of T1 to 95% of baseline was 7.6 min. There were no differences in the duration of recovery room stay for patients receiving succinylcholine or mivacurium.

Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers

UNLABELLED Administration of sevoflurane in a circle absorption system generates Compound A, a nephrotoxin in rats. Reports examining the potential of Compound A to produce renal injury in humans have provided conflicting results. We tested the possibility that there is a threshold to Compound A-induced renal injury in humans and that, above this threshold, renal injury increases with increasing doses of Compound A. Eleven volunteers received 3% sevoflurane for 8 h at 2 L/min, and three volunteers received 3% sevoflurane for 8 h at 4-6 L/min. We measured inspired and expired concentrations of Compound A and urinary excretion of albumin, alpha-glutathione-S-transferase (GST), and glucose. The median urinary excretion of albumin, glucose, and alpha-GST for the first 3 days after anesthesia increased significantly from preanesthetic values in the 2-L/min group. Compound A doses < 240 ppm-h resulted in normal urinary excretion of albumin, glucose, and alpha-GST. Five of seven subjects who received doses > 240 ppm-h had abnormal excretion of albumin, and six of seven had abnormal alpha-GST urinary excretion (P < 0.05). Urinary excretion of albumin, alpha-GST, and glucose was normal by 14 days after exposure. We conclude that sevoflurane administration for 8 h at 2 L/min results in albuminuria and enzymuria when the dose of Compound A exceeds 240 ppm-h. That is, a Compound A concentration of 30 ppm breathed for > or = 8 h may produce transient renal injury. IMPLICATIONS We examined the dose-response relationship of sevoflurane/Compound A and urinary excretion of albumin, glucose, and alpha-GST. Sevoflurane exposure for 8 h at a 2-L/min inflow rate produces transient albuminuria and enzymuria in healthy volunteers when the dose of Compound A exceeds 240 ppm-h (30 ppm for 8 h).

Prostacyclin Mediation of Vasodilation Following Mesenteric Traction

Eight untreated patients (group I) and four patients who received ibuprofen preoperatively (group II) scheduled for elective abdominal aortic ancurysm repair were studied. Heart rate (HR); systolic, diastolic, and mean arterial pressure (MAP); systolic and diastolic pulmonary artery pressure; pulmonary capillary wedge pressure (PCWP); cardiac output (CO); and central venous pressure (CVP) were recorded pre-induction, before mesenteric traction, and 5, 15, and 30 min post-mesenteric traction. Plasma samples were obtained at these times for analysis of six-keto-prostaglandin Flα (PGF1α) concentration by radioimmunoassay. Group II patients received ibuprofen 12 mg/kg orally 11/2 h before surgery. Plasma samples from six group I patients and all group II patients taken 5 min after mesenteric traction were added to isolated helical strips of cat superior mesenteric arteries precontracted with norepinephrine (200 ng/ml) for analysis of reduction in developed force. In group I, abdominal mesenteric traction resulted in a significant decrease in MAP (P < 0.03) and SVR (P < 0.005) with an increase in CO (P < 0.05) at 5 min post-mesenteric traction. which returned to mean pre-mesenteric traction values by 30 min and a significant increase in PGF,α concentrations. There was a significant positive correlation between PGF,α and CO (P < 0.001) and a significant negative correlation between PGF,α and SVR (P < 0.01) at 5 min post-mesenteric traction. Post-mesenteric traction plasma samples added to the cat mesenteric artery preparation resulted in vasodilation, as demonstrated by a reduction in developed force of 0.563 ± 0.092 grams, as compared to the reduction by pre-mesenteric traction plasma values of 0.12 ± 0.11 grams (P < 0.01). Group II patients did not develop significant increases in PGF,α, and 5-min post-mesenteric traction plasma samples did not significantly relax the cat mesenteric artery preparations. There were no changes in MAP, SVR, and CO in group II patients. Flushing of the head and neck in association with mesenteric traction was noted in group I only.

Preoxygenation in the morbidly obese: a comparison of two techniques

Morbid obesity by increasing acidity and volume of gastric contents, as well as by increasing and intragastric pressure (l), increases the risk of pulmonary aspiration of gastric contents during general anesthesia. Rapid sequence induction of anesthesia with cricoid pressure can prevent this complication. Gold et al. (2) have shown that four vital capacity breaths of 100% 0, within 30 seconds elevates PaO, in non-obese patients as effectively as 5 min of tidal breathing of 100% 0,. Morbidly obese patients with altered lung volumes and diminished compliance, may respond differently to preoxygenation (3). We therefore compared two methods of preoxygenation in morbidly obese patients undergoing rapid sequence induction and intubation.

Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern?

Sevoflurane administration can result in increased serum inorganic fluoride ion concentrations, which have been associated with inhibition of renal concentrating ability.We measured serum fluoride levels, renal function, and recovery variables as a function of time in ASA grade I-III patients administered general anesthesia with isoflurane or sevoflurane for at least 1 h. Fifty patients were exposed to sevoflurane (<or=to2.4% inspired concentration) or isoflurane (<or=to1.9% inspired concentration) for maintenance of anesthesia as part of a multicenter trial. Blood was collected for determination of serum fluoride ion concentration, electrolytes, blood urea nitrogen, and creatinine at various time points pre- and postoperatively. Mean serum fluoride levels were significantly increased in sevoflurane versus isoflurane groups at all time points; the mean peak serum levels were 28.2 +/- 14 micro mol/L at 1 h for sevoflurane and 5.08 +/- 4.35 micro mol/L at 12 h for isoflurane. Sevoflurane-mediated increases in serum fluoride levels peaked at 1 h and, in general, decreased rapidly after discontinuation of the anesthesia. Three of 24 patients exposed to sevoflurane had one or more fluoride levels > 50 micro mol/L. One of these patients had a serum inorganic fluoride ion level > 50 micro mol/L at 12 h after sevoflurane, and an additional patient had fluoride levels > 33 micro mol/L for up to 24 h after sevoflurane discontinuation. Those two patients also demonstrated an increase in serum blood urea nitrogen and creatinine at 24 h after sevoflurane administration compared with baseline. The elimination half-life of serum fluoride ion was 21.6 h. The results of this study suggest the possibility of sevoflurane induced nephrotoxicity. (Anesth Analg 1996;82:1268-72)

Relationship between Benign Prostatic Hyperplasia and History of Coronary Artery Disease in Elderly Men

Study Objective. To assess the relationship between the occurrence of benign prostatic hyperplasia (BPH), an androgen‐dependent disease, and coronary artery disease (defined as history of coronary artery bypass grafting, coronary angioplasty, myocardial infarction) in elderly men.

Clinical pharmacology of pipecuronium bromide.

The neuromuscular blocking and cardiovascular effects of pipecuronium, in doses ranging 2--3 times its ED95, were evaluated in 46 patients during thiopental, fentanyl, N2O/O2 anesthesia. The neuromuscular blocking effect of pipecuronium was evaluated by recording of the mechanical twitch of the adductor pollicis muscle in response to stimulation of the ulnar nerve at the wrist. Heart rate, systolic and diastolic blood pressures, and cardiac output were noninvasively measured during the onset of the neuromuscular blockade and compared to a saline control group to separate the effect of anesthesia from those of pipecuronium.The mean ± SD time from administration of pipecuronium to 90% suppression of the first twitch (T1) of the tram-of-four was 2.6 ± 0.8, 2.0 ± 0.6, and 2.1 ± 0.6 min following the 70 μg/kg, 85 μg/kg, and 100 μg/kg dose, respectively. There was no significant difference between the different doses of pipecuronium in the time to 90% suppression of T1. In general, all three doses of pipecuronium provided good to excellent intubating conditions within 3 minutes after its administration. The time from the administration of pipecuronium to 5% recovery of T1 was 52.3 ± 18.2 min in the group given 70 μg/kg. This was significantly longer in patients given 85 μg/kg (71.9 ± 15.7 min) or 100 μg/kg (71.8 ± 22.1 min). Times to the start of recovery of T1 and to 25% recovery of T1 showed a similar significant pattern. In 2/3 of the patients, administration of neostigmine (2.5 mg) resulted in adequate recovery of muscle function within 10 minutes. Only patients with T1 recovery to less than 15% of control or a T4/T1 ratio of zero tended to take longer than 10 minutes for full recovery. Heart rate and systolic and diastolic blood pressures decreased significantly after the induction of anesthesia and during the onset of neuromuscular blockade. The hernody-namic variables, however, were similar between the three pipecuronium groups and a control group (N=16) that received only saline. Therefore, no cardiovascular changes could be attributed to pipecuronium when compared to the control group. Cardiac output did not change significantly over the time course of the study.Pipecuronium bromide produces a long-acting, nondepolarizing neuromuscular blockade. A dose of 70 μg/kg can be expected to provide good intubating conditions in 3 minutes with a clinical duration of approximately one hour. Larger doses (85 μg/kg and 100 μg/kg) may shorten the onset time and increase duration on average by 20 minutes. Higher doses are thus best reserved for procedures of long duration. Because no cardiovascular effects were observed with doses ranging from 2--3 times its ED95, pipecuronium can be recommended for patients in whom cardiovascular stability is desired.

Comparison of atracurium and d-tubocurarine for prevention of succinylcholine myalgia

We compared the incidence of postoperative myalgia (POM) and fasciculations when atracurium (ATR) or d-tubocurarine (DTC) was given prior to succinylcholine (SDC) for tracheal intubation in 44 ASA class I or II outpatient females undergoing laparoscopy. The subjects were assigned to one of three groups: group 1 received 0.025 mg/kg ATR; group 2 received 0.05 mg/kg DTC; and group 3 received saline (NS), all in a double-blind manner. Thiopental was administered 1 min and 45 sec after pretreatment in doses adequate to allow control of ventilation. Three minutes after pretreatment, SDC 1.5 mg/kg was given, and fasciculations were recorded on a scale of 0-3. All patients were questioned 1 and 3 days postoperatively about POM, using a scale of 0-3. Fasciculations occurred in 79% of patients given saline, in 46% of those receiving ATR, and in 12% of those given DTC. Eighty-five percent of ATR patients were free of POM on postoperative day 1. The corresponding figures for DTC and NS were 59% and 43%, respectively. Only the difference between ATR and NS achieved statistical significance. On the third postoperative day, POM was rare and there were no significant differences among the groups. We conclude that DTC is a better defasciculant than ATR. DTC was, however, not significantly better than NS in the prevention of POM. The findings suggest that ATR may be the drug choice for the prevention of POM.

Clinical Pharmacology of Propofol: An Intravenous Anesthetic Agent

Propofol is a 2,6-diisopropylphenol with sedative-hypnotic properties. Because of its slight solubility in water, the drug is formulated as an emulsion for clinical use. It is highly lipophilic and distributes extensively in the body. The blood concentration-time profile of propofol after an iv bolus injection follows a three-compartment model with half-lives of 2–4 min, 30–45 min, and 3–63 h, respectively. Propofol is extensively metabolized by the liver prior to its elimination by the kidney. Following an iv dose of 2–2.5 mg/kg, loss of consciousness occurs in less than one minute and lasts for approximately five minutes. Hypnosis can be maintained by propofol blood concentrations of 1.5–6 μg/mL in the presence of N2O/O2 (60:40 ratio) or other anesthetic agents. During induction, propofol decreases the systolic and diastolic blood pressure by approximately 20–30 percent with minimal change in heart rate; apnea is also common. The cardiovascular and respiratory effects of propofol, however, should not cause major concern in otherwise healthy patients. By virtue of its pharmacokinetic profile, the drug lends itself to continuous infusion for maintenance of anesthesia. When used as the main anesthetic agent, it produces satisfactory anesthesia with rapid recovery and without major adverse effects in healthy individuals. In continuous infusion propofol can be used as an alternative to inhalation anesthetics.

Priming with atracurium

Priming with atracurium was evaluated by dividing 39 patients into 2 groups. All received 0.2 mg IV glycopyrrolate and fentanyl, 50 μg IV. Group 1 received saline, group 2 received 0.06 mg/kg atracurium and a stop watch was started. After 3.5 min the patients were asked to lift their heads and maximum negative inspiratory pressure (MIP) was measured. Anesthesia then commenced with thiorpental and a twitch monitor was applied to the ulnar nerve. At 5 min group 1 received 0.36 mg/kg atracurium and group 2 was given 0.30 mg/kg atracurium. At 6.5 min intubation was accomplished in all but one patient in group 1 and all but one in group 2. Mean T4/T1 ratios at 90 sec were 0.73 in group 1 and 0.51 in group 2. This difference was statistically significant (P < 0.001). Bucking on the endotracheal tube occurred in 72% of patients in group 1 and 62% of those in group 2 (not significant). Intubating conditions were “excellent” in 56% of those in group 1 and 75% in group 2 (not significant). “Good” conditions were seen in 33% of group 1 and 15% of group 2 patients (not significant). “Fair” conditions were noted in 6% of patients in group 1 and 5% of group 2 patients (not significant). The time to maximum twitch depression was 11.3 min and 11.5 min in groups 1 and 2 respectively (not significant). All patients in group 1 could sustain head lift whereas four patients in group 2 could not (not significant). A decrease in MIP was noted in 38% of patients in group 2, but MIP was not decreased in those in group 1. This difference was statistically significant (P < 0.005). We conclude that priming with atracurium, although providing a small improvement in T4/T1 ratio at intubation, does not significantly improve intubating conditions. It is complex, time consuming, is not well tolerated, and may put patients at risk for aspiration.