J.G. Whitwam

Specific Enhancement by Fentanyl of the Effects of Intrathecal Bupivacaine on Nociceptive Afferent But Not on Sympathetic Efferent Pathways in Dogs

BackgroundBupivacaine alone, or in combination with opioids, has been shown to provide adequate pain relief without motor paralysis. This study examined the effects of bupivacaine administered intrathecally on sympathetic efferent and Aδ- and C-fiber-mediated afferent pathways in dogs and the interactions with intrathecal fentanyl. MethodsSpontaneous activity in renal sympathetic nerves was observed, as were reflex somatosympathetic responses mediated by Aδ and C fibers evoked by supramaximal electrical stimulation of the tibial and radial nerve. Bupivacaine was administered intrathecally in doses of 0.5, 1, 2, and 3.5 mg, each in 0.5 ml, and 7 mg in 1 ml with or without pretreatment with 5.4 mg intrathecal fentanyl (ED25 for depression of C tibial reflexes) in each of five preparations. ResultsBupivacaine caused a dose-dependent inhibition of both Aδ- and C-fiber-mediated somatosympathetic responses evoked by tibial nerve stimulation. The depression of radial and tibial nerve reflexes and spontaneous renal sympathetic activity was similar. Pretreatment with fentanyl (5.4 μg, intrathecally) depressed tibial C-fiber reflexes by only 23.8% without any significant effect on either tibial Aδ or radial Aδ and C fiber responses. Fentanyl markedly enhanced the effect of subsequent doses of bupivacaine on tibial Aδ and C reflexes without any additional effect on either spontaneous sympathetic activity or radial responses. ConclusionsIntrathecal bupivacaine has no selectivity for the afferent and efferent pathways, and intrathecal fentanyl acts synergistically to enhance the effect of bupivacaine on the afferent pathway without a measurable effect on sympathetic outflow.

The accuracy of pulse oximeters. A comparative clinical evaluation of five pulse oximeters.

The accuracy of five commercially available pulse oximeters was compared against arterial blood oxygen saturation, under similar clinical conditions. The oximeters had very similar performance in the clinically useful range of 80–100%, with a tendency slightly to underestimate the true saturation.

Induction of microcurrents in critically ill patients in magnetic resonance systems.

To determine whether electric current can be induced in intracardiac catheters, thermistor wires and pacing electrodes in patients duringmagnetic resonance imaging (MRI). Design:Prospective laboratory study. Setting:Postgraduate medical school hospital. Subjects:A sheep heart model. Interventions:None. Measurements and Main Results:Voltage generated by saline 0.9% flowing through a magnetic field and distribution of current from a catheter tip within a sheep heart model were measured in a 0.15 Tesla MRI system. Resistance of loops formed by pacing wires, a pacing electrode, and a thermistor wire were measured in saline 0.9%. Effects of rapidly changing magnetic fields and the movement of the beating heart on epicardial pacing wires were calculated theoretically. A flow of 200 mL/min of saline 0.9% induced a current of 0.1 microampere (uA) (at 0.15 Tesla). From magnetic resonance images we derived a current density of −0.004 μA/mm2 (at 0.15 Tesla). Internal resistance of pacing catheters and thermistor wires was >1 megaohm (MΩ). The maximum currents calculated (for a higher field strength of 1.5 Tesla) in a circuit formed by epicardial pacing wires were 80 μA, induced by the beating heart moving the wires through the magnetic field and 46 μA, induced by the rapidly changing magnetic fields. Conclusions:Current generated by flow of conducting fluid should be safe. Pacing catheters and thermistor wires should be safe if well insulated and disconnected from external electric connections. However, current induced in epicardial pacing wires may be a hazard, and precautions should be taken. External wire tips must be separated, insulated, and coiled to lie along the axis of the magnetic field. Electrocar-diography is required, and defibrillation equipment should be available. (Crit Care Med 1993; 21:1923–1928)

Clonidine Has Comparable Effects on Spontaneous Sympathetic Activity and Afferent Aδ– and C-fiber-mediated Somatosympathetic Reflexes in Dogs

Background:Clonidine, an α2-adrenergic agonist, has been studied as an adjunct or alternative to spinal opioids in the management of moderate to severe pain. This study examined the relative effects of clonidine on efferent spontaneous sympathetic activity and afferent Aδ and C fiber-mediated somatosympathetic responses. Methods:Spontaneous and evoked sympathetic activity in renal sympathetic nerves, mediated by Aδ and C fibers by means of supramaximal electrical stimulation of the radial and tibial nerves, were observed in anesthetized dogs. Incremental doses of clonidine were administered intrathecally or intravenously in each of five preparations followed by intravenous naloxone 2 mg and yohimbine 5 mg. Results:Both spontaneous sympathetic outflow and afferent Aδ– and C fiber-mediated somatosympathetic responses evoked by tibial nerve stimulation were depressed in a similar dose dependent manner by clonidine administered intrathecally or intravenously in a dose ratio of approximately 1:4. Intrathecal clonidine inhibited and eliminated both local spontaneous sympathetic outflow and tibial nerve evoked sympathetic responses but had no significant depressant effect on the radial nerve evoked sympathetic reflexes. When administered intravenously clonidine had a similar depressant effect on both radial and tibial nerve elicited reflexes and spontaneous sympathetic activity. Conclusions:Clonidine, administered intrathecally or intravenously, has a similar depressant effect on both spontaneous sympathetic outflow and afferent Aδ– and C fiber–mediated somatosympathetic reflexes. When administered intrathecally it has little effect on reflexes evoked via the descending pathway by radial nerve stimulation.

Acute Tolerance to Fentanyl during Anesthesia in Dogs

The effect of fentanyl on increases in heart rate and mean arterial pressure elicited by electric stimulation of a branch of the radial nerve was studied in anesthetized, paralyzed, and artificially ventilated dogs. In one group, a bolus of 100 μg/kg of fentanyl depressed the evoked changes in heart rate and arterial pressure by 82 and 75%, respectively, by 5 min, and recovery occurred within 90 min. A second group was given increasing bolus doses of fentanyl from 1.5 to 100 μg/kg every 20 min for 200 min. The doses and intervals were chosen to give a logarithmic increase in plasma concentration of fentanyl to include a final bolus dose of 100 μg/kg and were predicted by a two-compartment pharmaco-kinetic model derived from data of the first group. In the second group, the bolus dose of 100 μg/kg after 5 min had no significant effect on evoked cardiovascular responses. Over the following 2 h, the evoked changes in heart rate and arterial pressure increased above those preceding the 100 μg/kg dose. An additional bolus dose of 100 μg/kg given 2 h after the first did not depress the evoked reflexes below the control values. It was concluded that tolerance to the effects of fentanyl can occur within 3 h and that for evoked responses to arterial pressure, rebound withdrawal effects can be seen within an additional 90 min.

Relative effects of intrathecal administration of fentanyl and midazolam on aδ and c fibre reflexes

The effects of fentanyl and midazolam, administered intrathecally, on somatosympathetic reflexes evoked by tibial nerve stimulation were investigated in 12 anaesthetized and paralysed dogs. Fentanyl depressed both the C and A delta fibre evoked reflexes in a dose ratio of approx 1:2. In contrast, midazolam had a greater effect on A delta compared with C fibre reflexes; while A delta reflexes were abolished by a total dose of 3 mg midazolam, C fibre reflexes were depressed by only 50%. The effect of fentanyl was reversed by naloxone (2 mg, i.v.) and that of midazolam by flumazenil (1 mg, i.v.). The results suggest that fentanyl and midazolam have different relative effects on A delta and C fibre pathways.

The uptake of isoflurane during anaesthesia.

The uptake of isoflurane at a constant end‐expired concentration of 1.5% in oxygen was studied in 15 women, ASA 1 or 2, undergoing elective total abdominal hysterectomy. The anaesthetic was administered by a simple computer‐controlled to‐and‐fro closed system. After an initial period of wash‐in to the system, the rate of uptake of isoflurane decreased bi‐exponentially with a rapid reduction during the first 15 min. Perturbations from this bi‐exponential decline reflect changes in cardiac output. The mean (SD) cumulative use of isoflurane was 4.5 (0.43) ml after 30 min and 7.3 (0.79) ml after 60 min.

A computer-controlled closed anaesthetic breathing system.

We describe the design and working of a computer‐controlled, closed anaesthetic breathing system which rapidly achieves and maintains a prescribed end‐tidal concentration ofisoflurane in oxygen. The system is simple to set up and not expensive; the only nonstandard component is a modified glass syringe. We have demonstrated that gas analysers may contribute as much as the patient to the accumulation of nitrogen within the breathing system. Details of our clinical experience with the system are presented in an accompanying article.

specific Actions of Halothane, Isoflurane, and Desflurane on Sympathetic Activity and A [greek small letter delta] and C Somatosympathetic Reflexes Recorded in Renal Nerves in Dogs

BackgroundThis was a study of the relative effects on directly recorded sympathetic activity of desflurane, isoflurane, and halothane.MethodsRenal sympathetic nerve activity (RSNA) was recorded with bipolar electrodes in renal nerves exposed retroperitoneally in anesthetized ([Greek small letter alp

The effect of sevoflurane on spontaneous sympathetic activity, A delta and C somatosympathetic reflexes, and associated hemodynamic changes in dogs

This study examined the effect of sevoflurane on spontaneous renal sympathetic nerve activity (RSNA), A delta-and C-fiber-mediated somatosympathetic reflexes, and hemodynamic changes in anesthetized dogs. RSNA, and A delta and C reflexes evoked by electrical stimulation of the radial nerve were observed in multifiber recordings of efferent activity in renal sympathetic nerves. Sevoflurane was administered at 1%, 2%, 3%, and 4% end-tidal concentrations for periods of 20 min. The mean A delta reflexes decreased by 20%, 39%, and 54% (P < 0.05 to < 0.01), and the C reflexes decreased by 38%, 62%, and 74% (P < 0.05 to < 0.01) at concentrations of 2%, 3%, and 4%, respectively. The relatively greater effect on C reflexes was significant (P < 0.05) and comparable with the effect of [micro sign]-opioids. There was no change in mean RSNA, heart rate (HR), and cardiac output (CO) up to 3% sevoflurane, but these decreased by 36%, 24%, and 13% (P < 0.05), respectively, at 4% sevoflurane. Sevoflurane 1%-4% caused a virtually linear reduction in systemic vascular resistance (SVR) from 7% (P < 0.05) to 44% (P < 0.05), together with a reduction in mean arterial pressure (MAP) that was significant for concentrations greater than 2%. The results indicate that sevoflurane causes a greater depression of C compared with A delta reflexes, and that the reduction in MAP was entirely due to a decrease in SVR up to 3%, whereas at 4% sevoflurane, reductions in sympathetic activity, HR, and CO also contributed its depressor effect. Implications: The relatively greater depressant effect of sevoflurane on C compared with A delta nociceptive somatosympathetic reflexes is similar to [micro sign]-opioids. The hypotensive effect of sevoflurane was significant at 2% concentration, whereas heart rate, cardiac output and sympathetic activity were reduced only at concentrations greater than 3%. (Anesth Analg 1998;86:1079-83)