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.

Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium.

Three clinically used anticholinesterases--neostigmine, pyridostigmine, and edrophonium--were tested for their ability to reverse two levels (60% and 95%) of neuromuscular blockade produced by pancuronium. A controlled in vitro environment of the rat diaphragm-phrenic nerve system was used for the studies. Concentrations of anticholinesterases spanned the clinical range and were extended beyond to establish dose-response curves. Neostigmine was the most potent reversal drug (ED50 for 95% block 5.5 +/- 4 nM), followed by pyridostigmine (0.27 +/- 0.06 microM) and edrophonium (2.1 +/- 0.05 microM). The three drugs were equally effective at reversal of block and fade as measured by train-of-four stimulation. The dose-response curves for all three drugs showed a ceiling effect for reversal of tension and fade. Supraclinical concentrations of drug did not effect complete reversal, especially at 95% block. High concentrations of anticholinesterase led to randomly appearing hyperactivity manifested by spontaneous twitching and repetitive firing with severe fade on stimulation.

Recovery of neuromuscular function in the perfused rat diaphragm after succinylcholine and pancuronium blockade.

The recovery of the rat diaphragm from neuromuscular blockade was studied in order to separate the contributions of drug binding and tissue washout. The in vitro rat diaphragm preparation was perfused with a cholinesterase-free solution via the phrenic vein and stimulated electrically via the phrenic nerve. Muscle paralysis was induced by infusion of a depolarizing blocker succinylcholine or by the nondepolarizing blocker pancuronium. The time for recovery from 25-75% recovery averaged 1.0 +/- 0.1 min for pancuronium and 0.8 +/- 0.1 min for succinylcholine at the fast (1.9 ml/min) perfusion rate. This was prolonged to 2.0 +/- 0.3 min for pancuronium and 1.4 +/- 0.1 min for succinylcholine at the slower (0.76 ml/min) rate. More sensitive paired tests of recovery utilizing recovery time and rate demonstrated no drug difference in three comparisons and a 44% longer recovery time for pancuronium only at the lower perfusion rate. In general, recovery times were similar for both drugs. The rapid recovery from pancuronium blockade in this mammalian system as perfusion rate was increased suggests that recovery from this drug is not impaired by drug binding but is strongly dependent on organ perfusion.

Relationship between train-of-four ratio and first-twitch depression during neuromuscular blockade: a pharmacokinetic/dynamic explanation.

Fade, as measured by train-of-four, lags behind twitch depression during the initial phase of nondepolarizing neuromuscular blockade, i.e., the ratio of the fourth to first twitch height in a train (T4/T1) is greater at the onset of the block than during spontaneous recovery for the same level of first twitch depression. We believe that these data can be explained by picturing the muscle as having localized regions that respond much more slowly than the rest, leading to a delay in drug effect in that area, especially when the drug concentration rises rapidly as during bolus administration. This was modeled by computer as a muscle of 15 compartments distributed in a log-normal fashion according to equilibration rate. Experimental data consisting of the time course of first twitch and train-of-four ratio were fitted by nonlinear regression to the model. A good fit was obtained with a median equilibration time t1/2 of 3.3 min and a standard deviation of 2.1. The difference between train-of-four during onset and regression of block at the same level of first twitch depression was reproduced.

Pancuronium, unlike other nondepolarizing relaxants, retains potency at hypothermia.

The authors studied the pharmacodynamics of four nondepolarising relaxants, d-tubocurarine (dTC), pancuronium, metocurine, and gallamine, at 25 degrees C, 31 degrees C, and 37 degrees C. The rat phrenic nerve-hemidiaphragm preparation with vascular perfusion was used for these investigations. For each drug at each temperature, a dose-response curve for twitch depression was constructed. ED50 values were calculated using probit-log dose regression. dTC, metocurine, and gallamine each demonstrated a near twofold increase in ED50 at 25 degrees C compared with 37 degrees C. No such relationship was apparent with pancuronium. In addition, the slopes of the dose-response curves were analyzed for effects due to temperature or drug. Slopes were not influenced by temperature; however, the slopes for metocurine and dTC were lower than those for pancuronium and gallamine. The authors conclude that in the rat, pancuronium retains potency at hypothermia, whereas the other relaxants decrease potency. In addition, metocurine and dTC exhibit less steep dose-response curves under these experimental conditions.