Said S. Azad

Rocuronium Onset of Action: A Comparison with Atracurium and Vecuronium

The onset, maximal neuromuscular block, and duration of rocuronium were compared with atracurium and vecuronium during enflurane anesthesia. Sixty patients received rocuronium (80,100,120, or 160 μg/kg). Enflurane enhanced a rocuronium neuromuscular block in a dose-related manner; the ED50 was 104 ± 11 and 83 ± 7 μg/kg (SEM) during 1% and 2% enflurane anesthesia, respectively. Patients receiving atracurium (0.12 mg/kg) or vecuronium (0.02 mg/kg) were studied during 1 % enflurane anesthesia until seven in each group qualified by achieving a maximal block between 85% and 97%. These patients were matched with each other and with patients who had received rocuronium. Seven groups of three patients (rocuronium, vecuronium, and atracurium) were obtained. The average difference in maximal block was less than 2% between matched patients. The ratio of dose used to achieve a similar final block suggests potency ratios of 1,8.5, and 1.2 for rocuronium, vecuronium, and atracurium. Rocuroniums onset time (time from drug administration to 50%, 75%, and 90% of final block) was significantly faster than either of the other two muscle relaxants (P < 0.01). Time to 90% of final block was 1.35 min for rocuronium, 3.06 min for atracurium, and 3.71 min for vecuronium. Using these equipotent doses, atracurium also had a shorter time to develop neuromuscular block than vecuronium (P < 0.05). For these three intermediate duration neuromuscular blockers, speed of onset was inversely related to their potency, confirming a relationship that had been demonstrated for the long-acting drugs pancuronium, d-tubocurarine, and gallamine.

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.

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.

The effect of the prone position on venous pressure and blood loss during lumbar laminectomy

STUDY OBJECTIVE To determine the effects of three different prone support systems (Andrews spinal surgery frame, Cloward surgical saddle, and longitudinal bolsters) on inferior vena cava (IVC) and superior vena cava (SVC) pressures; the validity of measuring central venous pressure (CVP) for the determination of ideal positioning of the patient; and the relationship among frame type, blood loss, and hemodynamic measurements. DESIGN Prospective, randomized study of the hemodynamic effects of the prone position. SETTING Inpatient surgery at a university hospital (regional spinal cord injury treatment center). PATIENTS Eighteen patients free of significant coexisting disease (ASA physical status I and II) undergoing elective lumbar laminectomy. INTERVENTIONS Patients were assigned to one of three support frames and measurement of SVC pressure, IVC pressure, and mean arterial pressures (MAP) were obtained supine, prone, and after repositioning. These pressures and measured blood loss were obtained every 15 minutes during the surgical laminectomy portion of the procedure. MEASUREMENTS AND MAIN RESULTS Patients positioned on the Andrews frame had decreased mean SVC and IVC pressures from 8.7 mmHg and 8.4 mmHg in the supine position to 3.3 mmHg and 1.8 mmHg in the prone position, respectively (p less than 0.001). Prone position CVP also was significantly lower in the Andrews group compared with that in the other two groups (p less than 0.001). Repositioning efforts did not significantly decrease CVP. Blood loss was higher in the Cloward group (1,150 +/- 989 ml) than in the Andrews (245 +/- 283 ml) and bolsters (262 +/- 188 ml) groups (p less than 0.02). CONCLUSIONS Increased blood loss was not associated with increased SVC or IVC pressure, nor was there any significant correlation between any demographic or hemodynamic variable and blood loss. There was no evidence that CVP is useful in determining the ideal prone position in patients undergoing lumbar laminectomy.

Intravenous labetalol for the treatment of hypertension after carotid endarterectomy

Hypertension after carotid endarterectomy has a variable incidence ranging up to 56%. Blood pressure (BP) control is essential due to possible increased risk of morbidity from neurologic deficits or cardiovascular complications. This study evaluated intravenous labetalol for control of hypertension after carotid endarterectomy. Sixty ASA II-IV patients were studied; 20 developed BP high enough for treatment with labetalol. The anesthetic technique was standardized. Labetalol was administered at the conclusion of surgery as a 20-mg bolus over two minutes followed by 40 mg every 10 minutes until the desired BP was achieved (BP less than or equal to 10% above average preoperative BP or less than 150 mmHg, systolic) or 300 mg had been given. The mean total dose of labetalol was 42.0 +/- 33.0 mg (mean +/- SD) and mean time to reach the desired BP was 16.2 +/- 21.4 minutes. Systolic, diastolic, mean arterial pressure and heart rate significantly decreased after labetalol treatment and remained so for the remainder of the 180-minute study period. There was no hypotension, bradycardia, evidence of myocardial ischemia or central nervous system dysfunction present with labetalol treatment. Blood samples were obtained for determination of plasma renin activity, epinephrine, and norepinephrine in 10 patients who developed hypertension and received labetalol, and 10 patients who did not develop hypertension. In the patients developing hypertension, there was a significant elevation in epinephrine just before treatment, that decreased by 30 minutes after treatment. Norepinephrine levels became significantly elevated five minutes after labetalol treatment in the group with hypertension and remained elevated for 120 minutes. Concomitantly, there was a significantly lower plasma renin activity seen in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of labetalol and nitroprusside for inducing hypotension during major surgery.

The hemodynamic and intrapulmonary shunt effects of intravenous labetalol and nitroprusside were compared during induced hypotension for major spinal surgery. A randomized, double-blind protocol was used in which 20 patients, ASA physical status I or II, received either nitroprusside infusion (n = 10) or labetalol bolus injections of 10 mg every 10 min (n = 10) until mean arterial blood pressure was reduced to 55--60 mm Hg. Pulmonary artery pressures were measured and mixed venous samples obtained via a pulmonary artery catheter. Nitroprusside increased heart rate significantly more than labetalol during the period of hypotension. When compared with prehypotension baseline values, nitroprusside increased heart rate significantly with a concomitant significant decrease in systemic vascular resistance. Cardiac output increased significantly 60 min after hypotension was achieved in patients treated with nitroprusside. Systemic vascular resistance decreased significantly below baseline levels in patients treated with labetalol but without changes in cardiac output, heart rate, or mean pulmonary artery pressure. There was a 122% increase in intrapulmonary shunt with nitroprusside administration, compared with an 11% increase with labetalol. Labetalol was effective for inducing hypotension and was not associated with an increase in heart rate, intrapulmonary shunt, or cardiac output as seen with nitroprusside.

A comparison of desflurane and isoflurane in prolonged surgery

STUDY OBJECTIVE To compare desflurane with isoflurane in several anesthetic situations. DESIGN Intubating conditions, hemodynamic response to intubation, maintenance hemodynamics, and speed of recovery from desflurane and isoflurane anesthesia were evaluated. In addition, interaction with a muscle relaxant at low and high concentrations of the anesthetics were compared. SETTING Thomas Jefferson University Hospital. PATIENTS Thirty-two patients who received general anesthesia for lengthy, mostly orthopedic procedures. INTERVENTIONS Immediately after induction with thiopental sodium, desflurane or isoflurane in nitrous oxide-oxygen was administered via face mask. Anesthesia was deepened until end-tidal concentration reached 1.7 minimum alveolar concentration (MAC). The trachea was intubated without the aid of a muscle relaxant. Heart rate (HR) and blood pressure (BP) were recorded before and at 1, 2, 4, 5, and 10 minutes after intubation. Noninvasive cardiac output (CO) and systemic vascular resistance (SVR) were determined while the patient was awake, immediately before intubation, and at 5 and 10 minutes after intubation. Following intubation, the concentration of desflurane or isoflurane was lowered until the end-tidal concentration reached 0.65 MAC (low-MAC group), 1.25 MAC (high-MAC group), or 0 MAC (control group). Pancuronium bromide in 0.005 mg/kg doses was administered incrementally until T1 (first twitch of train-of-four) was depressed more than 90%. ED50 and ED95 for pancuronium with balanced anesthesia and for desflurane or isoflurane in low and high MACs, as well as speed of recovery, were determined. The time to responsiveness and awakening also was determined. MEASUREMENTS AND MAIN RESULTS There was no significant difference between desflurane and isoflurane in intubating conditions or in BP or HR response to tracheal intubation. Both anesthetics increased HR significantly during induction. BP rose with desflurane at the preintubation point; other points showed no difference. A hyperdynamic response of increased HR and BP above 20% of baseline values was seen more frequently with desflurane (n = 7) than with isoflurane (n = 1). CO was elevated at all times after induction for low and high concentrations of both drugs, while SVR decreased over the same time with no significant difference between drugs. ED50 and ED95 for pancuronium were similar under desflurane and isoflurane at both low and high MAC, but they were significantly lower than under balanced anesthesia. Awakening times were similar for desflurane and isoflurane. CONCLUSIONS Desflurane is similar to isoflurane in providing anesthesia for intubation and maintenance. Desflurane tends to increase HR and occasionally causes a hyperdynamic response during rapid deepening of anesthesia. It is very similar to isoflurane in its interaction with pancuronium.

A dose-response evaluation of pipecuronium bromide in elderly patients under balanced anesthesia.

Pipecuronium bromide is a new steroidal non‐depolarizing muscle relaxant currently under investigation. It is similar to pancuronium with respect to the duration of action, but lacking its cardiovascular side effects. We examined the dose‐response relation of pipecuronium in 27 patients, ages 66–79 years, utilizing the incremental dose method under balanced anesthesia. The ED50, ED90 and ED95 were 22.42 (5.2) mcg/kg, 31.81 (6.9) mcg/kg and 35.12 (7.8) mcg/kg, respectively (log probit method). Our recovery data also demonstrate that residual neuromuscular blockade due to pipecuronium can easily be antagonized with neostigmine as long as spontaneous recovery of T1 at the time of reversal administration is >13%. The authors conclude that under balanced anesthesia the cummulative dose‐response of pipecuronium in the elderly patients is consistent with those previously described for younger population. Therefore, no dose adjustment appears necessary for the elderly. However, as with all medications, careful administration is appropriate.

Intubating Conditions after Pipecuronium Bromide: The Influence of Dose and Time

STUDY OBJECTIVE To determine the intubating conditions following the administration of pipecuronium bromide in doses of two (0.07 mg/kg) or three (0.1 mg/kg) times ED95 (average dose that gives 95% block of the first twitch). DESIGN To compare intubating conditions at 11/2 and 21/2 minutes in 41 patients receiving balanced anesthesia. SETTING Surgical patients at Thomas Jefferson University Hospital. PATIENTS Forty-one patients undergoing surgical procedure who received general anesthesia. INTERVENTIONS After obtaining a stable baseline of train-of-four (TOF), 41 patients randomly received either 0.07 mg/kg or 0.1 mg/kg of pipecuronium as a single intravenous (IV) bolus dose, and the trachea was intubated either at 11/2 or 21/2 minutes. MEASUREMENTS AND MAIN RESULTS Intubating conditions at 21/2 minutes appeared significantly better than those at 11/2 minutes, regardless of the pipecuronium dose. The mean time for T1 (first twitch of TOF) to reach 50% and 90% suppression was 1.36 +/- 0.51 minutes and 2.29 +/- 0.8 minutes, respectively, for the 0.07 mg/kg dose and 1.07 +/- 0.27 minutes and 1.72 +/- 0.45 minutes, respectively, for the 0.1 mg/kg dose. This did not make a significant difference in intubating conditions at either time. The time to 25% recovery of T1 was 68.2 +/- 22 minutes for the 0.07 mg/kg dose and 121.5 +/- 49 minutes for the 0.1 mg/kg dose. In patients who had spontaneous recovery of T1 to between 10% and 25% of control, administration of neostigmine or edrophonium resulted in identical recovery in 10 minutes. However, in patients with less than 10% spontaneous recovery of T1, neostigmine appeared to be superior to edrophonium. CONCLUSION Pipecuronium has a relatively rapid onset. The trachea could be intubated successfully in 11/2 minutes with a dose of either 0.07 mg/kg or 0.1 mg/kg. If the clinical situation requires perfect relaxation with no movement or bucking, we recommend waiting at least 21/2 minutes.

Junctional rhythm can mimic air embolism during precordial Doppler monitoring.

Venous air embolism (VAE) is a recognized complication of neurosurgical procedures performed in the sitting position. Although less common, VAE may also occur in the prone, supine, and lateral positions (1). Monitoring of precordial Doppler heart sounds has been advocated for early detection of venous air embolism (2). The following case report describes how a change in precordial Doppler sounds produced by a junctional rhythm may mimic those caused by VAE.