Oxide-oxygen Anaesthesia Research Articles

An Early Example of Evidence-based Medicine

Diffusion anoxia. By Bernard Raymond Fink. Anesthesiology 1955; 16:511-14. In 1955, Dr. Bernard Raymond Fink published his findings that described the mechanism by which hypoxemia occurred when nitrous oxide-oxygen anesthesia was discontinued and room air breathing commenced. Using an ear oximeter and brachial artery blood gases, he measured oxygen saturation in eight healthy patients who had received 75% nitrous oxide-25% oxygen for gynecologic surgery. He showed that oxygen saturation decreased from 5% to 10% and often reached a value below 90% when the patient began room air breathing after the nitrous oxide-oxygen was discontinued. The effect was seen over a 10-min period. He concluded that "anoxia arises because the outward diffusion of nitrous oxide lowers the alveolar partial pressure of oxygen." This phenomenon can become a causative factor of cardiac arrest in patients with impaired pulmonary or cardiac reserves.

Total intravenous anaesthesia with ketamine–midazolam versus halothane–nitrous oxide–oxygen anaesthesia for prolonged abdominal surgery

Total intravenous anaesthesia (TIVA) with ketamine-midazolam (KM) can be used for prolonged abdominal surgery. We compared this technique with halothane-nitrous oxide-oxygen anaesthesia using haemodynamic and endocrine stress responses as primary outcomes and adequacy of operating conditions and recovery profile as secondary outcomes. Fifty adult patients undergoing radical cystectomy and bladder substitution were randomly assigned to receive either TIVA with KM (n = 25) or halothane, nitrous oxide and oxygen anaesthesia (n = 25). Invasive haemodynamic and oxygenation variables were monitored along with plasma cortisol and growth hormone concentrations. Operative conditions and recovery profiles were registered. Cardiac index and vascular resistance remained stable during and after surgery. Cortisol concentrations doubled during surgery and remained elevated in the recovery period. Growth hormone increased after induction, peaked during surgery and decreased during recovery. Neither the haemodynamic variables nor the plasma hormone concentrations differed significantly between the two groups. Intestinal loops were collapsed in the KM groups providing better operative conditions and a reduced need for postoperative analgesics. The stress responses during KM anaesthesia for prolonged abdominal surgery were comparable to those during halothane-nitrous oxide-oxygen anaesthesia. However, KM anaesthesia provided better surgical conditions and better recovery.

Total intravenous anaesthesia with ketamine-midazolam versus halothane-nitrous oxide-oxygen anaesthesia for prolonged abdominal surgery

Background and objective: Total intravenous anaesthesia (TIVA) with ketamine-midazolam (KM) can be used for prolonged abdominal surgery. We compared this technique with halothane-nitrous oxide-oxygen anaesthesia using haemodynamic and endocrine stress responses as primary outcomes and adequacy of operating conditions and recovery profile as secondary outcomes. Methods: Fifty adult patients undergoing radical cystectomy and bladder substitution were randomly assigned to receive either TIVA with KM (n = 25) or halothane, nitrous oxide and oxygen anaesthesia (n = 25). Invasive haemodynamic and oxygenation variables were monitored along with plasma cortisol and growth hormone concentrations. Operative conditions and recovery profiles were registered. Results: Cardiac index and vascular resistance remained stable during and after surgery. Cortisol concentrations doubled during surgery and remained elevated in the recovery period. Growth hormone increased after induction, peaked during surgery and decreased during recovery. Neither the haemodynamic variables nor the plasma hormone concentrations differed significantly between the two groups. Intestinal loops were collapsed in the KM groups providing better operative conditions and a reduced need for postoperative analgesics. Conclusions: The stress responses during KM anaesthesia for prolonged abdominal surgery were comparable to those during halothane-nitrous oxide-oxygen anaesthesia. However, KM anaesthesia provided better surgical conditions and better recovery.

B. Raymond Fink at Columbia: A Personal Memoir

by Robert M. Epstein, lvI.D. Harold Carron Professor of Anesthesiology My first memories of Ray Fink follow his arrival at the Columbia-Presbyterian Medical Center in the summer of 1952, right after the start of my residency and the conclusion of his own at the Beth Israel Hospital in New York. The residents wondered, was this new at­ tending, barely two years ahead of us but fifteen years older? We learned quicldy that he was no usual retread! Only la ter did I discover the com­ plexities of Ray's background: from South Af­ rica, years in the United Kingdom, general prac­ tice of medicine. What unfolded for us was the pleasure of experiencing a man of questioning and creative imagination who had much to of­ fer his students and colleagues. Ray watched his patients closely. During his initial year he noted that blood oxygen desaturation during emergence from nitrous oxide-oxygen anesthesia was more common than most of us realized. It was easy to attribute this to partial obstruction or drug effects, but Ray-never satisfied with glib explanations­ thought physiologically. His velY earliest career days (presentation at the Federation meetings by the spring of 1954) thus saw the identifica­ tion of what he called diffusion anoxia. This important theory, of the effects of large volume gas exchanges during unsteady states, was the earliest identified of a group of similar effects, including the concentration and second gas ef­ fects found by others. My personal experience of Ray was inter­ rupted by militmy service in the Far East and by a return for two years of residency comple­ tion and research fellowship. After 1957 we were faculty members together for about seven years. For Ray they were years marked by an explo-

I.v. clonidine: does it work as a hypotensive agent with inhalation anaesthesia?

In a double-blind, randomized, placebo-controlled study, 41 patients received clonidine 3 micrograms kg-1 or placebo at induction of isoflurane and nitrous oxide in oxygen anaesthesia. Metoprolol was also given to achieve a systolic arterial pressure of 80 mm Hg. Requirements for metoprolol were significantly less in the clonidine group (P < 0.00035), with no significant difference in mean arterial pressures over time. It would appear that clonidine is an i.v. hypotensive agent worthy of consideration, but data during the recovery period are required to comment further on the safety of this technique.

Saline as an alternative to air for filling the laryngeal mask airway cuff

We have assessed a new method to evacuate saline completely from the laryngeal mask airway (LMA) cuff and tested the hypothesis that intracuff pressures, fibreoptic position and oropharyngeal leak pressures are similar for saline compared with air during nitrous oxide-oxygen anaesthesia. Eight size 4 LMA were inflated with saline 30 ml. After syringe evacuation, median residual weight was 0.56 (range 0.24-0.98) g; after additional manual cuff squeezing it was 0.26 (0.21-0.35) g; and after drying for 12 h at 60 degrees C with the valve open it was -0.02 (-0.05-0.04) g. Pressure-volume curves of four size 3-5 LMA showed that compliance was lower for the saline-filled cuff. A clinical study of 20 patients allocated randomly to have saline or air in the cuff showed a significant increase in intracuff pressure with air, but not saline, during nitrous oxide-oxygen anaesthesia. The fibreoptic position of the LMA changed more frequently in the air, compared with the saline-filled group (four of 10 vs none of 10; P = 0.04). Oropharyngeal leak pressures were similar between groups. We conclude that the saline-inflated LMA cuff was reliably emptied and more stable in terms of intracuff pressures and possibly fibreoptic position. Filling the LMA cuff with saline is a viable option during laser surgery to the airway.

Uptake of Halothane and Isoflurane by Mother and Baby During Caesarean Section

Twenty-three patients undergoing Caesarean section received either 0.5% halothane or 0.8% isoflurane to supplement nitrous oxide-oxygen anaesthesia. We studied the rate of uptake of the agents by the mother and fetus by measuring partial pressures in maternal arterial (Pa) and fetal umbilical venous (Puv) blood. Mean induction-delivery interval did not differ between the halothane (10.8 min) and isoflurane (11.7 min) groups. There were no differences in maternal heart rate, arterial pressure, pH and blood-gas tensions and fetal pH, blood-gas tensions or Apgar scores between the two groups. Isoflurane uptake by the mother was more rapid than halothane; at delivery, mean Pa of isoflurane as a fraction of the inspired partial pressure (Pl) was 0.44 compared with 0.35 for halothane (P < 0.05). Mean Puv as a fraction of maternal Pa at delivery was 0.71 for both agents; thus placental transfer was the same for both agents. Consequently mean Puv/Pl was greater for isoflurane (0.32) than halothane (0.26) (P < 0.05). We conclude that both halothane and isoflurane are suitable agents for general anaesthesia for Caesarean section. The rate of uptake of isoflurane by the mother during Caesarean section was more rapid than halothane. The rate of uptake by the fetus from the mother was the same for halothane and isoflurane, so that fetal partial pressure as a fraction of the inspired partial pressure was greater for isoflurane than halothane.

Time course of potentiation of mivacurium by halothane and isoflurane in children

We studied 40 children, aged 1-15 yr, to analyse the time course of potentiation of mivacurium produced by halothane and isoflurane. A steady infusion requirement of mivacurium to maintain 90% neuromuscular block was established during thiopentone-alfentanil-nitrous oxide-oxygen anaesthesia. Patients were then allocated randomly to receive 1 MAC end-tidal concentration of either halothane (group Hal) or isoflurane (group Iso) while neuromuscular block was maintained at 90%. Both volatile agents decreased the infusion requirements of mivacurium in an exponential manner in that maximal potentiation occurred only after 30-80 min. Maximal reduction in infusion rate (32% in group Hal and 70% in group Iso; P < 0.0001) did not depend on the age of the child but became established sooner the younger the child in the case of isoflurane (P = 0.002).

Comparative potency of steroidal neuromuscular blocking drugs and isobolographic analysis of the interaction between rocuronium and other aminosteroids

We have determined the relative potency of rocuronium, pancuronium, pipecuronium and vecuronium, and examined the nature of the interaction of rocuronium with the other three steroidal neuromuscular blocking drugs. We studied the dose-response relationships of each drug and their combination with rocuronium in 200 ASA I or II patients during propofol-fentanyl-nitrous oxide-oxygen anaesthesia. Neuromuscular block was recorded as the evoked thenar mechanomyographic response to single twitch stimulation of the ulnar nerve at 10-s intervals. The dose-response curves were determined by probit analysis. Isobolographic and algebraic (fractional) analyses were used to assess the combined effect of equipotent doses of rocuronium and vecuronium, pipecuronium or pancuronium and to define the type of interaction between these drugs. The isobolograms were constructed by plotting single-drug ED50 points on the dose co-ordinates, and a combined ED50 point in the dose field. The calculated doses producing 50% depression (ED50) of the twitch height for rocuronium, pancuronium, pipecuronium and vecuronium were 144.8 (95% confidence intervals 140.4-149.3), 32.4 (31.7-32.9), 27.1 (26.5-27.6) and 23.7 (22.7-24.8) micrograms kg-1, respectively. Corresponding doses producing 95% depression (ED95) of twitch height were, respectively, 322.1 (307.5-337.3), 58.1 (56.2-60.1), 48.7 (46.9-50.5) and 39.9 (38.4-41.4) micrograms kg-1. Based on the estimate of ED50, the relative potency was 1:4.5:5.4:6, respectively. The interaction between rocuronium and vecuronium, pipecuronium or pancuronium was found to be additive.

Pharmacokinetics and pharmacodynamics of the three isomers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function

We have studied the pharmacokinetics of cis-trans, trans-trans and cis-cis mivacurium in nine healthy patients (creatinine clearance 66-133 ml min-1), in seven patients with end-stage renal failure requiring dialysis (creatinine clearance 4-11 ml min-1) and in seven patients with impaired renal function (creatinine clearance 32-49 ml min-1), during thiopentone-fentanyl-midazolam-nitrous oxide-oxygen anaesthesia. Mivacurium chloride was infused at a rate of 15 micrograms kg-1 min-1 for 10 min, 7.5 micrograms kg-1 min-1 for a further 10 min, and then at a rate adjusted to maintain T1/T0 at 5%. The minimum duration of infusion was 60 min (range 60-235 min). The plasma concentration of the three isomers was measured at regular intervals throughout the infusion, and for up to 300 min after the infusion was stopped. Compartmental analysis of the resulting isomer profiles was undertaken: one- and two-compartment models were fitted to derive clearance, volume of distribution and terminal elimination half-life. Clearance of the cis-cis isomer was reduced significantly in the renal failure (median 2.4 (range 2.1-2.6) ml kg-1 min-1) and intermediate renal function groups (2.1 (2.0-2.9) ml kg-1 min-1), compared with healthy patients (3.8 (2.6-4.9) ml kg-1 min-1) (P < 0.01 in each case).(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of halothane and isoflurane by mother and baby during Caesarean section

Twenty-three patients undergoing Caesarean section received either 0.5% halothane or 0.8% isoflurane to supplement nitrous oxide-oxygen anaesthesia. We studied the rate of uptake of the agents by the mother and fetus by measuring partial pressures in maternal arterial (Pa) and fetal umbilical venous (Puv) blood. Mean induction-delivery interval did not differ between the halothane (10.8 min) and isoflurane (11.7 min) groups. There were no differences in maternal heart rate, arterial pressure, pH and blood-gas tensions and fetal pH, blood-gas tensions or Apgar scores between the two groups. Isoflurane uptake by the mother was more rapid than halothane; at delivery, mean Pa of isoflurane as a fraction of the inspired partial pressure (Pl) was 0.44 compared with 0.35 for halothane (P < 0.05). Mean Puv as a fraction of maternal Pa at delivery was 0.71 for both agents; thus placental transfer was the same for both agents. Consequently mean Puv/Pl was greater for isoflurane (0.32) than halothane (0.26) (P < 0.05). We conclude that both halothane and isoflurane are suitable agents for general anaesthesia for Caesarean section. The rate of uptake of isoflurane by the mother during Caesarean section was more rapid than halothane. The rate of uptake by the fetus from the mother was the same for halothane and isoflurane, so that fetal partial pressure as a fraction of the inspired partial pressure was greater for isoflurane than halothane.

Auditory steady-state response, upper facial EMG, EEG and heart rate as predictors of movement during isoflurane-nitrous oxide anaesthesia

We have studied the relationship between patient movement and changes in the auditory steady-state evoked potential, upper facial muscle electromyogram (FEMG), electroencephalographic-zero crossing frequency (EEG-ZCF) and heart rate during emergence from anaesthesia. Twelve healthy patients underwent surgery during stable isoflurane-nitrous oxide-oxygen anaesthesia without neuromuscular block. After skin closure, anaesthesia was discontinued abruptly while mechanical ventilation was continued until the patient moved. The magnitude of change in each physiological signal was evaluated in decibels (dB). Both the auditory steady state evoked potential and FEMG showed significant increases in amplitude during the last 5-min period before movement (6.1 and 10.7 dB, respectively). EEG-ZCF increased rapidly after anaesthesia was discontinued (2.5 dB) but there was no further increase in activity before movement. Heart rate did not change before movement. The use of the decibel transformation offers a promising method of displaying and interpreting changes in physiological variables during anaesthesia.

Laryngeal mask airway cuff pressure and position during anaesthesia lasting one to two hours.

The cuff of the laryngeal mask airway (LMA) is highly permeable to nitrous oxide (N2O), and cuff pressure increases during N2O/O2 anaesthesia. The extent of these changes and their effect on LMA position have previously only been investigated for short procedures. The current study was designed to investigate the effects of nitrous oxide-oxygen (N2O/O2) anaesthesia lasting one to two hours on cuff pressure, LMA positioning and pharyngeal morbidity. Twenty-four male patients underwent spontaneous ventilation anaesthesia with 66% N2O in oxygen and isoflurane. Following insertion and inflation of a #4 LMA with 30 ml air, mean (SD) cuff pressures immediately increased from 107 (9) to 145 (12) mmHg and then at a decreasing rate for 90 min to peak at 215 (12) mmHg. There was a correlation between N2O concentration and final cuff volume (P < 0.001). There was no displacement of the LMA cuff in any patient. Three of 19 patients had a mild sore throat. This study demonstrates that the increase in LMA cuff pressure is self limiting over a one-to-two-hour period and does not cause displacement of the LMA. There is no evidence that cuff pressure monitoring and pressure limitation is necessary during LMA anaesthesia.

Respiratory sinus arrhythmia: comparison with EEG indices during isoflurane anaesthesia at 0.65 and 1.2 MAC

Respiratory sinus arrhythmia (RSA) is a cyclical variation in heart rate during breathing, where the heart rate increases during inspiration and decreases during expiration. RSA and the electroencephalogram (EEG) were monitored in 10 patients undergoing elective surgery with isoflurane and nitrous oxide in oxygen anaesthesia after induction with propofol. All patients were subject to controlled ventilation and recovery from competitive neuromuscular block was facilitated by neostigmine and glycopyrronium (seven patients) or atropine (three patients). Median and spectral edge (95%) frequencies of the raw EEG were derived off-line. RSA and EEG indices were obtained during preinduction (baseline), induction, incision, 0.65 and 1.2 MAC of isoflurane maintenance during surgery and recovery. Significant decreases in the level of RSA, median and spectral edge frequencies were observed during induction and significant increases in all indices were observed at recovery in all patients. Significant decreases in the median and spectral edge EEG frequencies occurred in patients treated with atropine both to counteract bradycardia after propofol induction and at antagonism of neuromuscular block (n = 3), compared with patients treated with glycopyrronium (n = 7). In contrast, the level of RSA did not decrease significantly with atropine. It is concluded that measurements of RSA could form the basis of a useful index of anaesthetic depth during isoflurane anaesthesia, even during the use of pharmacologically appropriate doses of atropine. However, any effects of atropine on the raw EEG and on indices derived from the EEG, should be characterized further so that these effects are not confused with changes in anaesthetic depth.

The Neuromuscular Effects of ORG9426 in Patients Receiving Balanced Anesthesia

In searching for a nondepolarizing muscle relaxant with intermediate duration but more rapid onset of action than the presently available compounds, the neuromuscular and circulatory effects of ORG9426 were investigated in two studies in humans receiving fentanyl, droperidol, thiopental, and nitrous oxide-oxygen anesthesia. Eighty patients, randomly assigned to one of four groups of 20 each, received 0.12, 0.16, 0.20, or 0.24 mg/kg ORG9426. In the first study, the doses (in milligrams per kilogram) of ORG9426 that caused 50% (ED50), 90% (ED90), or 95% (ED95) neuromuscular block were determined by the individual dose-response method; they were 0.170, 0.268, and 0.305 mg/kg, respectively. In the second study, after induction of anesthesia, patients received 0.6 mg/kg (about 2 x ED95) of ORG9426, either in a single bolus (group 1) or in two unequal (0.1 and 0.5 mg/kg) increments 4 min apart (group 2). After the administration of 0.6 mg/kg ORG9426, maximal neuromuscular block developed in 1.5 +/- 0.12 min in group 1 and in 1.2 +/- 0.14 min in group 2. Patients tracheas were intubated after development of the maximal neuromuscular effect of the intubating dose and after the recording of heart rate and systolic and diastolic blood pressure. There was no difference in the clinical duration of the intubating doses, which were 40.0 +/- 3.2 (15-73) min in group 1 and 39.3 +/- 2.4 (19-57) min in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Local anesthesia blocks the antiemetic action of P6 acupuncture

The incidence of postoperative illness was monitored for 6 hours in 74 women premedicated with nalbuphine, 10 mg, and undergoing short gynecologic operations of similar duration under methohexitalnitrous oxide-oxygen anesthesia. Each patient received P6 acupuncture for 5 minutes at the time of administration of premedication. In random order the site of the acupuncture had been previously infiltrated with normal saline solution in half of the patients and 1% lidocaine in the remaining patients. Postoperative emetic sequelae occurred significantly more often in those who received lidocaine compared with the group that received saline solution. This demonstrates the ability of a local anesthetic administered at the point of stimulation to block the antiemetic action of P6 acupuncture in a manner similar to that shown by others for analgesia.

The effect of peripheral hypothermia on a vecuronium‐induced neuromuscular block

Seven healthy patients were investigated during midazolam-fentanyl nitrous oxide-oxygen anaesthesia. The mechanical twitch response of the adductor pollicis muscle was recorded simultaneously during bilateral supramaximal train-of-four (TOF) stimulation of the ulnar nerves at the wrist. Intense neuromuscular block was evaluated using the post-tetanic count (PTC) method. Core temperature and the peripheral skin temperature of one arm were kept normal and stable. Following cooling of the other arm to a peripheral hand skin temperature of 27 degrees C, vecuronium was administered in a bolus dose of 0.05 mg.kg-1 followed by maintenance doses of 0.02 mg.kg-1. In the hypothermic and the normothermic arm the onset time following the bolus dose was 180 +/- 40 (mean +/- s.d.) seconds and 140 +/- 30 s, respectively, the duration of action was 26.4 +/- 4.5 and 16.5 +/- 4.0 min and the recovery time was 265 +/- 90 and 130 +/- 60 s (P less than 0.01). The time course of action following maintenance doses showed a similar marked difference between the hypothermic and the normothermic arm. In the normothermic arm a close correlation was found between the number of post-tetanic twitches and the time to first response to TOF stimulation. In contrast, in the hypothermic arm the number of post-tetanic twitches showed great variation with a poor correlation to the duration of intense neuromuscular block. It is concluded that the time course of action of a vecuronium-induced neuromuscular block is markedly prolonged during peripheral hypothermia and intense neuromuscular block cannot reliably be assessed using the PTC method at low peripheral temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

麻酔の聴性誘発反応に及ぼす影響

Auditory brainstem response (ABR) and auditory middle latency response (MLR) in 128 patients were recorded during the surgical operation which was performed under the various anesthetic methods and conditions. The relation between the anesthetic methods and the characteristics of the auditory evoked responses was investigated. From the results, the anesthesia could be classified into following three types: type A such as enflurane-nitrous oxide-oxygen and halothane-nitrous oxide-oxygen anesthesia by which both ABR and MLR were affected, type B such as thiamylal and diazepam anesthesia by which only MLR was affected, and type C such as neuroleptanesthesia (NLA), high dose fentanyl, ketamine, althesin, spinal and epidural anesthesia, by which both ABR and MLR were not affected. Therefore, when ABR and MLR are recorded as a monitor of the eighth nerve surgery, NLA would be the most adequate and available method. On the other hand, it was proved that ABR and MLR were markedly affected by the decrease of body temperature. Therefore, the decrease of body temperature should be taken into consideration when the auditory evoked response of comatose patients was monitored.

CARDIOVASCULAR EFFECTS OF DOXACURIUM, PANCURONIUM AND VECURONIUM IN ANAESTHETIZED PATIENTS PRESENTING FOR CORONARY ARTERY BYPASS SURGERY

The cardiovascular effects of bolus doses of doxacurium 0.037 mg kg-1 were compared with those following equipotent doses of pancuronium (0.09 mg kg-1) and vecuronium (0.075 mg kg-1) and with those following high-dose doxacurium (0.075 mg kg-1), in patients with coronary artery disease. Anaesthetic technique comprised premedication with lorazepam, papaveretum and hyoscine, induction with diazepam, fentanyl, thiopentone, atropine and suxamethonium, and the trachea was intubated. At least 20 min later, during stable nitrous oxide in oxygen anaesthesia, a single bolus of neuromuscular blocking drug was administered and the effects measured at 1, 5 and 10 min. There was a small decrease in heart rate following doxacurium 0.075 mg kg-1, but no other significant or dose-related changes in mean heart rate, arterial pressure or cardiac index with doxacurium. Similar results were found following vecuronium, but the reduction in heart rate was more pronounced. In contrast, significant increases in mean arterial pressure, heart rate and cardiac index occurred after pancuronium.

Cerebrospinal Fluid Pressure in Patients With Brain Tumors

The effects on the cerebrospinal fluid pressure (CSFP) of alfentanil and fentanyl were compared during nitrous oxide-oxygen (N2O-O2) anesthesia in 24 patients who had brain tumors. Monitored variables included CSFP (lumbar subarachnoid catheter), heart rate from electrocardiographic lead II, mean radial arterial blood pressure, and arterial blood gas tensions. General anesthesia was induced with thiopental, 5 mg/kg IV in divided doses, and maintained with 70% N2O in O2; ventilation was held constant (PaCO2 = 37.4 +/- 1.6 mm Hg [mean +/- SEM]). After baseline data were recorded, 16 subjects were randomly assigned to receive either 5 micrograms/kg fentanyl as an intravenous bolus or 50 micrograms/kg alfentanil as an intravenous bolus, followed by an infusion of alfentanil at 1 micrograms.kg-1.min-1. Monitored variables were continuously recorded for 15 min after opioid injection. A third group of 8 patients was studied subsequently; they received only N2O-O2 during a 15-min observation period and served as controls. Blood pressure was held constant with an intravenous infusion of 0.1% phenylephrine, as needed; noxious stimulation was carefully avoided. Cerebrospinal fluid pressure remained unchanged both in patients who received N2O-O2 alone and in those who received fentanyl-N2O-O2. By contrast, those who received alfentanil-N2O-O2 had a gradual increase in CSFP, reaching 30% above baseline values after 10 min and stabilizing thereafter. Although the absolute increase in CSFP during normocarbic alfentanil-N2O anesthesia was relatively small (9.5 +/- 1.3 mm Hg to 13.0 +/- 1.3 mm Hg [mean +/- SE], P less than 0.05), the absence of a similar effect after fentanyl administration suggests that precautionary measures such as hyperventilation are advisable if alfentanil is used for potentiating normocarbic N2O-O2 anesthesia in neurosurgical patients with intracranial mass lesions.