Theodore J. Sanford

A comparison of morphine, fentanyl, and sufentanil anesthesia for cardiac surgery: Induction, emergence, and extubation

We compared anesthetic doses of three popular opiates, morphine (n = 10), fentanyl (n = 9), and sufentanil (n = 9) in patients undergoing cardiac surgery. Opiate administration after induction was based upon EEG and cardiovascular signs of the depth of anesthesia. Total doses were morphine, 4.4 ± 0.71 mg/kg, fentanyl, 95.4 ± 9.9 μg/kg, and sufentanil, 18.9 ± 2.2 μg/kg. Comparisons among opiates included times for induction of anesthesia, return of consciousness, return of spontaneous ventilation, return of adequate cardiovascular status, and extubation. The following times (mean and SEM) were significantly (P < 0.05) shorter for sufentanil than for fentanyl or morphine: induction (15 ± 2.3 min, 5.9 ± 0.7 min, and 3.0 ± 0.2 min for morphine, fentanyl, and sufentanil, respectively); return of consciousness (morphine 109.7 ± 34.4 min, fentanyl 62.3 ± 17.9 min, sufentanil 77 ± 8.7 min); return of acceptable and stable cardiovascular status (morphine 587.3 ± 239.3 min, fentanyl 537.9 ± 144.8 min, sufentanil 173.7 ± 56.8 min); and extubation (morphine 1122.3 ± 61.8 min, fentanyl 1005.7 ± 77.7 min, sufentanil 533.3 ± 67.8 min). We conclude that sufentanil administered in the dosage range of 19 μg/kg allows more rapid induction, earlier emergence from anesthesia, and faster extubation of patients than either morphine or fentanyl.

Physiology of Alfentanil-induced Rigidity

The authors investigated the hemodynamic, metabolic, electroencephalographic (EEG), and electromyographic (EMG) characteristics of narcotic-induced rigidity during induction of anesthesia with alfentanil (175 μg/kg) in 10 patients. Thiopental (4 mg/kg) was administered to a ten-patient control group. Rigidity was quantified in eight muscle groups (sternocleidomastoid, deltoid, biceps, forearm flexors, intercostal, rectus abdominus, vastus medialis/lateralis, and gastrocnemius). Marked rigidity was observed in all muscle groups in all patients receiving alfentanil and in none receiving thiopental. Central venous pressure increased with onset of rigidity, while mean arterial pressure and cardiac index remained unchanged. Manual ventilation was extremely difficult during alfentanil-induced rigidity. Arterial oxygen tension decreased more rapidly during rigidity than during the same time interval in the control group, while patients experiencing rigidity were more acidotic, as reflected by greater increases in base deficit. The EEG demonstrated an anesthetic state without seizure activity. The immediate increase in central venous pressure with the onset of rigidity, along with occasional simultaneous parallel variations in central venous pressure and the EMG, strongly suggest a mechanical mechanism for the change in central venous pressure. The metabolic changes during rigidity may be partly related to the absence of the normal cardiovascular reflexes that are reported to occur during voluntary isometric muscle contractions. A neurochemical mechanism of narcotic-induced rigidity is briefly reviewed.

EEGs during High-Dose Fentanyl-, Sufentanil-, or Morphine-Oxygen Anesthesia

In 49 patients undergoing open-heart surgery we compared the electroencephalographic (EEG) effects of high-dose morphine, fentanyl, or sufentanil with O2, using two computerized analysis and display techniques: a period analysis (the Klein method) and an aperiodic analysis (the Neurometrics monitor). During fentanyl or sufentanil anesthesia, both techniques revealed a general decrease in frequency, shown by the aperiodic analysis primarily as a marked increase in the very low frequency range: an increase in the 1-Hz bin (TP1, in μv2) from 2.80 × 104 ± 3.20 × 104 (SD) to 45.1 × 104 ± 27.2 × 104 for fentanyl and from 3.11 × 104 ± 2.83 × 104 to 52.8 × 104 for sufentanil. The cumulative percent power at 3 Hz (CP3) increased from 27.2 ± 6.8 to 83.0 ± 11.0 for fentanyl and from 22.7 ± 5.2 to 85.1 ± 10.4 for sufentanil, while the frequency at 90% cumulative percent power (F90, in Hz) decreased from 17.8 ± 2.9 to 7.9 ± 2.8 for fentanyl and 16.4 ± 5.2 to 5.6 ± 4.3 for sufentanil. The changes with morphine were less obvious, with some attenuation of high-frequency power shown by the Klein method, and an increase from 24.1 ± 8.6 to 59.3 ± 20.7 with CP3, but no change in TP1. Low-frequency power with the period analysis and TP1 with the aperiodic analysis decreased between laryngoscopy and the incisions with fentanyl and sufentanil. We conclude that these narcotics given in high doses markedly alter the EEG, that the changes with fentanyl and sufentanil are greater than those with morphine, that computerized analysis and display techniques can quantitate these changes, that--- using the EEG of other general anesthetics as a guide---the patients were adequately anesthetized, and that, given the appropriate variables, the EEG probably reflects the depth of anesthesia with high-dose narcotics.

Seizures during opioid anesthetic induction: are they opioid-induced rigidity?

The tape recorded EEGs of 127 patients anesthetized with large doses of opioids were retrospectively analyzed for evidence of opioid-induced seizures, and in particular, correlated with movements that occurred during induction and could be clinically interpreted as seizures. Bilateral EEG leads in patients receiving fentanyl (20), sufentanil (20), or alfentanil (87) were recorded. Forty-six of these patients from all opioid groups manifested intense rigidity, as assessed both clinically and by EMGs recorded from eight muscles in 69 of the patients receiving alfentanil. This intense rigidity often resembled seizures, in that the phenomenon entailed severe stiffness of both limbs and trunk, with an explosive onset of myoclonic limb movements, and associated vertical nystagmus. Electroencephalographic observations were extensive, entailing 69 h of paper recordings played back from the tapes, at paper speeds of 30 or 60 mm/s, with detailed annotations from the voice track. These paper recordings were examined in detail independently by three of the investigators, who were unaware of the clinical phenomena that had occurred. The only observed EEG activity that could have been interpreted as epileptiform consisted of small sharp waves related to muscle activity or other artifact. The EEG never indicated seizure activity during these drug-induced movements and rigidity. Reports of opioid-induced seizures are reviewed and a set of criteria is offered to help achieve future consistency and credibility in evaluating this phenomenon. The available evidence does not support the existence of opioid-induced seizures in the clinical setting.

An electroencephalographic comparison of alfentanil with other narcotics and with thiopental.

Using aperiodic analysis, we compared the EEC produced by alfentanil with the EEGs produced by two other opiates—fentanyl and sufentanil—on the one hand and with the EEG produced by a barbiturate—thiopental—on the other hand. Alfentanil and thiopental were injected over 1 minute: fentanyl and sufentanil were injected over 10 to 15 minutes. From the aperiodic analysis we derived up to seven single-number variables computed over 30- or 60-second epochs. All the opiates induced EEGs that were qualitatively similar to each other, although the maximum or minimum values tended to be greater and the time course more rapid with alfentanil than with the other two opiates. This finding may have been related to the fact that we injected relatively more alfentanil and administered it more rapidly. The EEGs produced by alfentanil and thiopental differed markedly, both qualitatively and quantitatively. The total power at 1 Hz and cumulative power at 3 Hz went to higher peak values with alfentanil, the latter tending to decrease with thiopental. The total number ot waves per epoch went to lower peak values with alfentanil; there was little change with thiopental. The frequency below which 90% ot the power resides went to considerably lower peak values with alfentanil than with thiopental. Finally, total power at 10 to 12 Hz (alpha waves; and average power at 17 to 19 Hz (beta waves) went to very high peak values with thiopental, but decreased with alfentanil. In spite ot differences in the opiate studies in the timing ot injection and the relative amount ot drug injected, the variables that proved useful in their response to fentanyl and sutentanil also proved useful with altentanil. In contrast, almost all variables showed a difference in response between alfentanil and thiopental.

Pulse oximetry and finger blood pressure measurement during open-heart surgery.

Pulse oximeter arterial hemoglobin oxygen saturation (SpO2) and finger arterial pressure (FINAP) were continuously monitored before, during, and after cardiopulmonary bypass in 15 male patients. SpO2 was monitored simultaneously with two pulse oximeters, a Nellcor N-100 and an Ohmeda Biox III. The readings obtained from the two pulse oximeters were compared with arterial blood measurements obtained using a CO-oximeter. FINAP was monitored by a prototype device (Finapres) based on the Peňaz volume-clamp method. FINAP was correlated with intraarterial pressure (IAP). Both pulse oximeters functioned well before cardiopulmonary bypass. The correlations with CO-oximeter values were 0.927 for the N-100 and 0.921 for the Biox III. Immediately after the onset of cardiopulmonary bypass, the N-100 pulse oximeter stopped displaying values. The Biox III pulse oximeter continued to display values during the cardiopulmonary bypass period; the correlation with CO-oximeter values was 0.813. After cardiopulmonary bypass, the N-100 began displaying values in 2 to 10 minutes. After cardiopulmonary bypass the correlation with CO-oximeter values was 0.792 for the N-100 and 0.828 for the Biox III pulse oximeter. The Finapres finger blood pressure device functioned well in 13 of 15 patients before cardiopulmonary bypass. The mean bias ± precision of FINAP-IAP for mean pressure was 8.3±10.2 mm Hg (SD) and the correlation coefficient was 0.814. During cardiopulmonary bypass, the Finapres device functioned well in 10 of 15 patients. The mean bias precision of FINAP-IAP, for mean pressure in these 10 patients was 6.6±8.7 mm Hg and the correlation coefficient was 0.902. Immediately after cardiopulmonary bypass, the Finapres functioned well in 11 of 15 patients. The mean bias ± precision of FINAP-IAP for mean pressure was 8.6±14.1 mm Hg and the correlation coefficient was 0.533. This study documented that devices for continuous noninvasive monitoring can usually function well under the extreme conditions seen during open-heart surgery. Pulse oximeters may find a place in the monitoring of patients during open-heart surgery, although they cannot totally replace the invasive techniques. Under the conditions of diminished pulsatile peripheral blood flow we observed some differences between the two pulse oximeters.

Fiberoptic stylet laryngoscope and sitting position for tracheal intubation in acute superior vena caval syndrome

Acute obstruction of the superior vena cava produces a clinical syndrome that includes acrocyanosis; engorgement and edema of the head, neck, and arms; and development of superficial collateral venous pathways (1). The edema may be sufficient to cause obstruction of airway and the venous congestion sufficient to render blind instrumentation of the nasopharyngeal and/or laryngotracheal regions dangerous because of possible hemorrhaging (2-4). We recently employed a semimalleable optical stylet (American Optical, Model SLS fiberoptic laryngoscope) to aid in establishment of a patent airway in a patient with severe symptoms due to obstruction of the superior vena cava.

Do dopaminergic drugs really prevent opiate-induced rigidity?

We were quite interested to see the recent letter (1) suggesting that amantadine, a drug that appears to stimulate release and inhibit reuptake of dopamine in the basal ganglia, may prevent fentanyl-induced muscle rigidity. Based on their clinical experience, Silbert and Vacanti raise some provocative questions. Given the complexity of the neuropharmacology of opiate rigidity and the limited animal data supporting a dopaminergic component to this form of muscle rigidity, it is unfortunate that the authors were only able to present a single case report. While we can not scientifically state that amantadine pretreatment does or does not attenuate opiate-induced rigidity, we have reason to be skeptical of the findings in a single patient. After having quantified rigidity using electromyography in over 100 patients (2,3) and several thousand rats, it is clear to us that there is tremendous individual variation in the expression of opiate rigidity. In addition, subjective assessment of rigidity does not always correlate well with either electromyographic or mechanographic measures. Last, Silbert and Vacanti’s patient received 10 mg of diazepam 1 hour before induction of anesthesia. Our human data (see Fig. 1) demonstrate that diazepam is relatively effective at attenuating alfentanilinduced rigidity. It is therefore possible that the failure of Drs. Silbert and Vacanti’s patient to exhibit rigidity could have been due to the diazepam premedication and not to the amantadine. The “pill rolling tremor” they describe is intriguing, although it is not uncommon for patients made rigid with alfentanil to exhibit coarse jerking arm and hand movements. It should be stressed that the neurochemical basis of opiate-induced rigidity is probably very different from that of phenothiazine-induced rigidity (4). The paper cited by Silbert and Vacanti (5) describes the role of a dopaminespecific neostriatal subregion in haloperidol (not opiate) rigidity. Several recent studies (6,7) failed to demonstrate any role for the neostriatum in opiate-induced muscle rigidity. Interestingly, the recent work of Jerussi et al. (8) suggests that neither dopamine agonists or antagonists are particularly effective at antagonizing fentanyl rigidity in rats. In fact, their study provides much stronger evidence for a-2 adrenergic involvement in opiate rigidity. Work in our laboratory has substantiated the hypothesis of others that brainstem sites containing serotonergic and GABAergic pathways play a crucial role in the expression of opiate rigidity (9,lO). We would also like to respond to the speculations regarding possible opiate-Parkinsonian interrelationships. MPTP, a “designer” meperidine derivative, produces Parkinsonism by destroying the dopaminergic cell bodies in the substantia nigra (11). The drug does not have any opioid activity (12). Despite the widespread use of high-dose opiates in anesthesia and chronic pain for many years, there have never been any reports (or even suggestions) of opia te-induced Parkinsonian symptoms. It is clear that the neurochemistry of opiate rigidity is complicated and multiple brain regions and transmitter pathways probably mediate this undesirable effect of highdose opiates. The selection of effective pretreatment regimens to prevent opiate rigidity must be based on a sound scientific foundation, begun in the laboratory and substantiated with controlled clinical trials. A single patient does not a study make.