Joaquin Cantillo

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).

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)

Fenoldopam infusion for the treatment of postoperative hypertension

STUDY OBJECTIVE To examine the safety and efficacy of intravenous fenoldopam as compared to placebo for the treatment of postoperative hypertension. DESIGN Randomized, placebo-controlled, double-blind study. SETTING Community hospital. PATIENTS 16 ASA I-III hypertensive patients scheduled for noncardiac surgical procedures. INTERVENTIONS Treatment with fenoldopam or placebo was initiated immediately after other causes of hypertension had been ruled out. Hypertension was defined as a supine systolic blood pressure (SBP) or diastolic blood pressure (DBP) greater than 20% over the patients preoperative baseline, which was obtained 6 hours prior to the procedure with the patient lying quietly. The baseline consisted of 3 consecutive blood pressure (BP) measurements obtained at 5-minute intervals and not varying by more than 10%. Fenoldopam or placebo infusion was initiated at 0.1 microgram/kg/min and increased and decreased as necessary until the therapeutic goal BP was reached or treatment failure had occurred. The therapeutic goal BP was a decrease to at least 10% above the preoperative baseline, and failure of treatment was defined as inability to reach this BP level after 15 minutes at 1.5 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS BP and heart rate (HR) data were collected consistently throughout the study and 1 hour after termination of infusion. Laboratory studies and 12-lead electrocardiographic results were obtained at the start of the study and repeated 24 hours after termination of infusion. Blood samples were obtained for the measurement of epinephrine, norepinephrine, and dopamine levels and were analyzed using high-performance liquid chromatography with electrochemical detection. Pretreatment BP measurements were significantly elevated from baseline in both groups. Fenoldopam treatment significantly reduced BP to the therapeutic goal in 8 of 8 patients; placebo reduced BP to this goal in only 4 of 8 patients (p < 0.05). At the end of the titration period, the therapeutic goal BP was not significantly different from baseline in the fenoldopam group. HR was significantly elevated (p < 0.05) at goal in the fenoldopam group as compared with the placebo group. Fenoldopam administration lowered SBP and DBP to goal in a mean time of 28 minutes versus 42.5 minutes in the placebo group. There were no significant differences in catecholamine levels at any of the measurement periods. CONCLUSION Fenoldopam is an effective drug for reducing BP following hypertensive episodes in the postoperative setting. Fenoldopam use is associated with an increase in HR versus placebo.

Perioperative arrhythmias with a propofol-based anesthetic

Propofol was used for the induction and maintenance of anesthesia in a patient undergoing a laparoscopic tubal ligation. This new anesthetic has not been associated with postoperative ventricular arrhythmias. This report demonstrates the occurrence of supraventricular tachycardia deteriorating to ventricular tachycardia in a patient who received propofol. Included is a discussion of the possible causes of this event.

Recovery parameters after sevoflurane and isoflurane anesthesia.

We compared recovery times in patients with American Society of Anesthesiologists physical status 1—III receiving sevoflurane or isoflurane during surgical procedures longer than 1 hour in duration. Of the 50 patients enrolled, 23 received sevoflurane and 27 received isoflurane. Anesthetic gases were discontinued abruptly at the end of the surgical procedure. The following parameters were recorded: time to emergence (opens eyes), time to extubation, response to verbal command (squeezes hand of observer), and orientation (time and place). Exposure times to the agents were similar. The time to emergence was significantly less with sevoflurane than with isoflurane (5.6 vs 11.2 min, respectively). There were no significant differences in time to extubation, response to verbal command, or orientation between the groups. Our data support more rapid emergence with sevoflurane than with isoflurane in surgical procedures longer than 1 hour in duration.

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.

Ventilatory Failures with the Datex-Ohmeda 7900 SmartVent

THE Datex-Ohmeda 7900 SmartVent (Madison, WI) is a microprocessor-controlled ventilator that is supplied with the Aestiva 3000 (Datex-Ohmeda) and the Excell 210 SE anesthesia machine (Datex-Ohmeda). It allows ventilation in two ventilatory modes: volume and pressure control. The ventilator is therefore capable of handling a wide range of patients, from neonates to patients with challenging procedures, such as thoracic and neuro-surgical. With a wide range of control and alarm settings, it can compensate for small leaks in the breathing circuit and compression losses. Recently, we had three cases in which the Datex-Ohmeda SmartVent failed to maintain the ventilatory settings, requiring swift intervention.

Difficult intubation from gastroesophageal reflux disease in adults.

Two cases of difficult intubation are presented. Both cases presented with red swollen arytenoids, swollen false vocal cords, and subglottic stenosis. Tracheal intubation could not be achieved for these reasons. Both patients were placed on gastrointestinal prokinetic drugs and histamine-two blocker, as a diagnosis of gastroesophageal reflux disease (GERD) was made. In one case, follow-up by an otolaryngotic surgeon showed reversal of the above findings. In the other case, one tracheal intubation was achieved eventually. GERD occurs frequently. Clinicians need to maintain a high index of suspicion for GERD-related airway changes so as to avoid potential difficult intubations.