EXTRADURAL ANALGESIA DURING LABOUR USING ALFENTANIL

Transcription

1 Br.J. Anaesth. (),, EXTRADURAL ANALGESIA DURING LABOUR USING ALFENTANIL L. HEYTENS, H. CAMMU AND F. CAMU Selective spinal analgesia (Cousins and Mather, ) with extradural opioids during labour has several advantages over extradural blockade using local anaesthetic drugs. It does not cause sympathetic blockade or motor paralysis of the lower limbs and should not, theoretically, lead to a higher incidence of instrumental delivery. However, different studies using extradural opioid analgesia during labour show considerable differences in the efficacy of the technique and the usefulness of the various drugs used (Crawford, ; Magora, Olshwang and Eimerl, ; Perriss, ; Carrie, O'Sullivan and Seegobin, ; Justins, Francis and Houlton, ; Justins, Knott and Luthman, 3). Furthermore, a major concern exists in regard to the potential for causing ventilatory depression in the newborn. In this study, alfentanil was chosen because of two pharmacokinetic characteristics: its high plasma protein binding (.% in the range - ng ml" ) and its short elimination half-life (Bower and Hull, ). Both decrease the risk of neonatal ventilatory depression when compared with the longer acting opioids. PATIENTS AND METHODS Patients Sixteen primiparous patients with an uncomplicated singleton pregnancy, and with the fetus presenting by the vertex were included in the study on requesting pain relief. All patients gave informed consent. They did not, at any time, receive a systemically administered narcotic drug. Sixteen newborn infants from primiparae who did not have an extradural (or any other form of L. HEYTENS, M.D., F. CAMU, M.D. (Department of Anesthesiology); H. CAMMU, M.D. (Department of Gynecology, Andrology and Obstetrics); Akademisch Ziekenhuis, Vrije Universiteit Brussel, Laarbeeklaan, Brussels, Belgium. Accepted for Publication: November 3,. Correspondence to L.H. SUMMARY Sixteen primiparous patients requesting pain relief during labour received a continuous infusion of alfentanil 3 ng kg- h~ x via an extradural catheter. Supplementary {extradural) bolus doses {3 ng kg~*) were administered when deemed necessary. Excellent pain relief was rapidly obtained early in labour in all patients. However, analgesia was inadequate in the latter part of stage I and during the second stage in five of the patientsnotwithstanding several additional doses of alfentanil, and bupivacaine had to be administered. No serious maternal side-effects, except nausea, were encountered. A/though all neonatal Apgar scores were between and, the Amiel-Tison test clearly indicated the existence of neonatal hypotonia. The continuous extradural administration of alfentanil proved to be unsatisfactory for pain relief in labour. analgesia) and with approximately the same duration of the first stage served as controls to assess any possible effect of alfentanil on the newborn. Clinical management Before inserting the extradural catheter (at the L3 space) a vaginal examination was carried out to obtain a reference Bishop score (Bishop, ). Intrauterine pressure was monitored subsequently in of the patients (fetal monitoring intrauterine pressure kit, Hewlett-Packard C, connected to a quartz transducer, Hewlett-Packard model A). Uterine activity was expressed in Montevideo Units (the sum of the amplitudes (in mm Hg) of the contractions occurring during a -min period (Caldeiro- Barcia and Poseiro, I)). A loading dose of alfentanil 3 ng kg~ l diluted

2 33 BRITISH JOURNAL OF ANAESTHESIA in saline to a total volume of ml was injected to the extradural space when the parturient first asked for pain relief. This injection was immediately followed by a continuous infusion of 3 ug kg" hr. Top-up doses (3 ug kg- ) were given when deemed necessary and. % bupivacaine ml was administered when the analgesia with alfentanil alone became inadequate. The infusion of alfentanil to the extradural space was stopped at the beginning of the second stage of labour. No further drugs were administered thereafter. Arterial pressure, heart rate and ventilation rate were measured every min for 3 min and, thereafter, at -min intervals or when clinically indicated. Maternal Pa co was measured in only four patients because of the inconvenience of arterial blood sampling in this setting. Assessment of pain The severity of pain was assessed every min during the first 3 min, and at -min intervals thereafter, using a numerical rating scale - ( = no pain at all, = worst possible pain). Recurrence of pain was considered significant when the new pain score was equal to or greater than % of the initial pain score. At that moment, a new bimanual vaginal examination was carried out to obtain information regarding the descent of the fetal head (ischial spine = ) and the rate of cervical dilatation (table II). Assessment of the newborn The newborn infants were assessed using the Apgar score at, 3, and min and the Amiel-Tison score at -3 min of life (Amiel- Tison, Barrier and Shnider, ). The same neurobehavioural tests were performed on the newborns which served as controls. Comparisons between the groups were analysed using the Kruskal-Wallis one-way analysis of variance. In six patients, maternal blood samples were taken at birth, together with arterial and venous blood samples from the umbilical cord to permit the measurement of alfentanil concentration (radioimmunoassay). RESULTS Patient characteristics The two groups were comparable with regard to maternal age and the duration of gestation (table I). The higher mean Bishop score in the control group can explain the shorter total duration of labour (Friedman et al., ). Pain scores The mean initial pain score was somewhat higher than we usually observe and this was probably because of the score of given by two patients. Pain relief was excellent within less than min TABLE I. Patient data (mean {range)). Control group Alfentanil group Number of patients Maternal age (yr) Duration of gestation (weeks) Dilatation at time of extradural (cm) Bishop score* Duration Phase I + Phase II (min).... (-3) (3-) (-) (-) (-33) (3-) (l-o) (3-) (-) * Bishop score = measure of inducibility of labour. Recorded at the moment the patient was included in the study. Includes evaluation of: Station of the presenting part Dilatation (cm) Enactment (cm) Consistency Position of os Rated as -3 - >. Firm Post. - Medium Central -/ + / + 3- Weak Anterior (Maximum = 3 patients) > <. 3

3 EXTRADURAL ALFENTANIL IN OBSTETRICS 333 TABLE II. Pain scores. * Pain considered significant if score > % of initial pain score, t Sum of the amplitudes (in mm Hg) of the contractions occurring during a -min period: a = before pain recurrence; b = when new significant pain score was recorded. X No intrauterint pressure monitoring. $ Patient : no pain recurrence {according to our criterion) Patient No. Initial pain score Recurrence of pain* Interval (min) Score Position (Ischial spine = ) Dilat- tdon (cm) Montevideo unitsf a b 3 3 Range - -s - - -? -/ - - / * * 3 * in all patients and remained acceptable for -. h (fig. ). No correlation could be found between the recurrence of pain (as denned above) and the degree of cervical dilatation, nor with the descent of the fetal head. However, recurrence of pain did coincide with an increase in uterine activity as expressed by the increase in Montevideo Units (table II). Satisfactory pain relief could be maintained in of the patients by injecting additional doses of alfentanil. Such supplements of alfentanil only helped when given early in labour; they did not provide adequate analgesia in the latter part of stage I. Five patients required supplements of extradural bupivacaine. Alfentanil requirements The wide range observed in total dose is explained by both considerable differences in the duration of the infusions and in the body weight of the patients (- kg), and the several supplementary doses given to some patients (table III). Maternal and neonatal plasma concentrations of alfentanil at birth No correlation was found between the duration of stage IIthe interval during which no alfentanil was givenand the neonatal plasma concentrations of alfentanil. The umbilical vein: umbilical artery ratio of alfentanil was greater than, denoting fetal uptake or metabolism, or both (table IV). Clinical effects and side-effects Drowsiness was reported by almost half the patients and occurred within - min of the injection (table V). However, cerebral cognitive functions remained normal throughout labour. Dizziness occurred in three patients but only within the first min of the injection. Itching, confined to the abdomen and legs, was reported by almost all patients, but elicited no spontaneous complaints. The incidence of nausea, excluding one patient receiving PGF a a, was %. No urinary retention was observed in patients; information regarding the other six patients was unavailable. Hypotension, defined as a decrease in systolic arterial pressure of greater than %, did not occur. Ventilation rate decreased significantly from preinjection values, but this could be TABLE III. Alfentanil requirements (mean (range)) Duration of infusion (min) Time from stopping infusion to delivery (min) Total dose (mg) Total dose (ug kg" ) Total dose (ug kg" h" ).3(-) 3. (-) 3.3 (.-.). (.-33.) 3. (.-.)

4 33 BRITISH JOURNAL OF ANAESTHESIA g o c Mean Range Pain score Mean.3 Range r Time (min) FIG.. Pain score (mean and range) v. time attributed to the effective analgesia and was never less than b.p.m. In four patients, arterial blood samples, drawn when analgesia was complete, revealed P*co, values between.3 and. kpa within the normal range for the parturient. Evaluation of the neonate As expected, theoretically, the duration of stage II was not prolonged in the alfentanil group compared with the control group. All the newborn infants had Apgar scores of or more at min (table VI). One baby in the control group had Apgar scores of, 3 and at, and min and this accounted for the lower mean Apgar score in the control group. Umbilical arterial and venous ph values were comparable in both groups. The total score on the neurological part of the Amiel-Tison test was significantly lower in the alfentanil group. This resulted from a lower score for passive (.) and active tone (.) than those recorded in the control group (passive:.3; active:.3). Further evaluation of the neonates by the paediatrician did not denote any abnormal feeding habits nor behavioural changes. TABLE IV. Maternal and neonatal plasma concentration of alfentanil at birth Patient No. Duration of stage II (min) Maternal concn (ng ml" ) Umb. vein (ng ml" ) Umb. an. (ng ml"') Umb. vein to maternal ratio

5 EXTRADURAL ALFENTANIL IN OBSTETRICS 33 TABL V. Side effects, f Excluding one patient who received PGF,a Drowsiness Dizziness Nausea/vomiting Itching Urinary retention Hypotension No. / 3/ / / / / / % f DISCUSSION The continuous extradural infusion of alfentanil was chosen for conduction analgesia during labour because of the short elimination half-life of alfentanil (Bower and Hull, ), and on account of the short duration of action of a single injection of the drug (preliminary trial). These facts, together with the low umbilical cord: maternal vein ratio of.3 (Bonnardot, 3), led us to believe that the administration of additional doses, when required, would not increase the likelihood of neonatal ventilatory depression. Excellent pain relief was invariably obtained within min after the injection of the loading dose of alfentanil; its high lipid solubility favoured rapid penetration of the dura. However, vascular uptake and transport via the posterior radicular artery or excretion through the arachnoid granulations in the dural cuff regions, or both, are important coexisting mechanisms (Cousins and Mather, ). Two characteristics of the pattern of pain relief in this study were of interest. First, no relationship could be found between the recurrence of pain and the position of the presenting part, or with the degree of cervical dilatation. This eliminated the possibility that recurrent abdominal (not perineal) pain, could be caused by central pain transmission via non-blocked nerves. On the other hand, there was a positive correlation, with an increase in Montevideo units or, in other words, with an increase in the contractile force of the uterus. Second, it was noted that the incremental doses resulted in transient improvements in analgesia when given fairly early in labour, and not at all when given late in the first stage of labour. The same phenomenon was seen in the preliminary trial when the loading dose was given late in stage one; pain relief remained inadequate even when alfentanil ug kg" was given. This indicated that there is an inherent maximal analgesic capacity for extradurally administered alfentanil; thus, when uterine activity exceeds a certain limit in any individual patient, the administration of alfentanil, in whatever dose, will not result in adequate pain relief. Other studies (Carrie, O'Sullivan and Seegobin, ; Justins, Francis and Houlton, ; Justins, Knott and Luthman, 3) demonstrated invariably the poor efficacy of extradural opioids during late stage I and during TABLE VI. Evaluation of the neonate. t Mean {range); % mean (SD). $ One control patient with Apgar scores, 3 and at, and min. Amiel-Tuon Score: adaptive capacity score omitted. **** P <.; *** P <. Time amniotomy to delivery (min) Duration second stage (min) Apgar score min 3 min min PH Venous Arterial Amiel-Tison scored Passive tone (max. ) Active tone (max. ) Primary reflexes (max. ) General assessment (max. ) Total score (max. 3) Control group. (-)t 33.3 (-)t.$ (l-)t. (3-). (-).3 (.-.3).(.-.3).3 ±.+.3 ±..±.3.3 ±.. ±.3+ Alfentanil group (-). (-). (-). (-). (-).3 (.-.3). (.-.3). ±.****. ±.***.±..±.3. ±.****

6 33 BRITISH JOURNAL OF ANAESTHESIA the second stage of labour. However, as supplementary doses were not administered, the possibility remained that an inadequate dose of opioid had been given in the first place. Our findings refute this possibility. It has been established that extradurally administered opioids exert their analgesic effect through a direct action upon the dorsal column and not centrally through intrathecal spread or vascular absorption (Kitahata and Collins, ; Yaksh, ). Side-effects, however, are caused by the systemic absorption of the opioid. The rapid onset of such effects seemed to indicate a relatively rapid uptake of the drug via the extradural venous plexus. Sedation was found to occur even before the onset of analgesia and to last throughout the period of the continuous infusion of alfentanil, although this effect was less apparent as analgesia became less complete. The lack of impairment of maternal cerebral function and the absence of complaints from the patients made us believe this side-effect was readily acceptable. The high incidence of nausea and vomiting was disappointing and probably resulted from the direct effect of alfentanil on the area postrema in the floor of the fourth ventricle. In two patients, small doses of naloxone were administered to abolish the vomiting. As analgesia remained unaffected, this observation supports the hypothesis that the analgesia attributable to alfentanil results from an extradural, and not a central, site of action. Itching has been reported to be frequent in parturient women (Scott, Bowen and Cartwright, ). Mild pruritis was reported by of the patients in this study, but only on direct questioning. This sensation was confined to the abdomen and legs and was not consistent with the usual finding of most severe itching in the palate and the face (Yaksh, ). Facial itching occurred in two patients immediately after the administration of a "top-up" dose. Although adequate Apgar scores were found in the alfentanil group, the Amiel-Tison test clearly demonstrated neonatal hypotonia. As this was not reflected by the Apgar score, the evaluation of the effects of intrathecal and extradural opioids during labour should include the more sensitive neurobehavioural tests. Neonatal hypotonia constituted one of the major, if not the major, drawback of the use of alfentanil as it could lead to serious problems if other compromising factors were present. The failure of opioid analgesia during the late stage I and stage II of labour could be caused by the transmission of pain via high-threshold neurones in lamina I which do not project on deeper laminae, but directly into the spinothalamic tract, thus bypassing the opioid u-receptors concentrated in the substantia gelatinosa (Bowsher, ; Yaksh, ). Alternatively, the observation that such different products as serotonin (Yaksh, ), baclofen (Yaksh, ) and midazolam (Whitwam, 3) can produce spinal analgesia, suggests that there are definite spinal systems mediating nociception, on which opioids cannot exert any influence. It may be that "selective spinal analgesia" during labour is "too selective" and that a combination of an opioid with a local anaesthetic agent will be necessary. ACKNOWLEDGEMENTS The authors thank Prof. J. J. Amy (Head, Department of Gynecology) for allowing us to carry out this study, the midwives for their co-operation, Janssen Pharmaceuticals for performing the alfentanil assays and Miss I. Rasschaert for her secretarial assistance. REFERENCES Amiel-Tison, C, Barrier, G., and Shnider, S. M. (). A new neurological and adaptive capacity scoring system for evaluating obstetric medications in full-term newborns. Anesthesiology,, 3. Bishop, E. H. (). Pelvic scoring for elective induction. Obsut. Gynecol.,,. Bonnardot, J. P. (3). Alfentanil et etomidate en obstetrique. Correlation des tame plasmatiques foeto-materaels a la naissance. Zentraleuropaischer Aniisthesiekongress, Zurich, Sept. 3-, 3. Bower, S., and Hull, C. J. (). Comparative pharmacokinetics of fentanyl and alfentanil. Br.J. Anaesth.,,. Bowsher, D. (). Pain pathways and mechanisms. Anaesthesia-, 33, 3. Caldeiro-Barcia, R., and Poseiro, S. (). Physiology of uterine contraction. Clin. Obsut. Gynecol., 3, 3. Carrie, L. E. S., O'Sullivan, G. M., and Seegobin, R. (). Epidural fentanyl in labour. Anaesthesia, 3,. Cousins, M. J., and Mather, L. E. (). Intrathecal and epidural administration of opioids. Anesthesiology,,. Crawford, J. S. (). Experiences with epidural morphine in obstetrics. Anaesthesia, 3,. Friedman, E. A., Niswander, K. R., Baysnet-Rivera, N. P., and Sachtleben, M. R. (). Relation of prelabor evaluation in inducibility and the course of labour. Obsut. Gynecol., M,. Justins, D. M., Francis, D., and Houlton, P. G. (). A controlled trial of extradural fentanyl in labour. Br. J. Anaesth.,,. Knort, C, and Luthman, J. (3). Epidural versus

7 EXTRADURAL ALFENTANIL IN OBSTETRICS.33 intramuscular fentanyl. Analgesia and pharmacokinetics in labour. Anaesthesia, 3, 3. Kitahata, L. M., and Collins, J. G. (). Spinal action of narcotic analgesics. Anesthesiology,, 3. Magora, F., Olshwang, D., and Eimerl, D. (). Observations on extradural morphine analgesia in various pain conditions. Br. J. Anaesth.,,. Perriss, B. W. (). Epidural pethidine in labour. A study of dose requirements. Anaesthesia, 3, 3. Scott, P. V., Bowen, F. E., and Cartwright, P. (). Intrathecal morphine as sole analgesic during labour. Br. Mtd.J.,,3. Whitwam.J. B.(3).Benzodiazepinereceptors.Anaesthesia, 3,3. ' Yaksh, T. L. (). The synergistic interaction of three pharmacologically distinct spinal systems mediating antinociception: the intrathecal action of morphine, serotonin and baclofen. Soc. Neuroses., (abstr.),. (). Spinal opiate analgesia: characteristics and principles of action. Pain,, 3.