Vergleichende Untersuchungen zur intravenösen Opioidanalgesie Sufentanil und Alfentanil zur extrakorporalen Stoßwellenlithotripsie bei urologischen Patienten

Zusammenfassung

In der prospektiven randomisierten Doppelblindstudie wurden 62 Patienten der ASA-Klassen I–II in zwei Gruppen verteilt. Gruppe I erhielt Sufentanil, Gruppe II Alfentanil zur intravenösen Analgesie bei extrakorporaler Stoßwellenlithotripsie (ESWL). Die Dosierung für Sufentanil betrug durchschnittlich 0,11 mg, für Alfentanil 4,2 mg. Untersucht wurden Blutdruckverhalten, transkutaner Kohlendioxidpartialdruck (P_tcCO₂) und Sauerstoffsättigung mittels Pulsoximetrie (spO₂) bei Spontanatmung mit O₂-Maske (6 l/min) vor und während der Behandlung und während 2 h postoperativer Aufwachraumzeit. Gleichzeitig erfolgten eine Eigenbeurteilung von Müdigkeit und Schmerz anhand der visuellen Analogskala (VAS) durch den Patienten sowie eine Beurteilung der Vigilanz und der Schmerzen durch den Anästhesisten (VAS). Nach Abschluß der Überwachungsphase erfolgte eine Gesamtbeurteilung durch den Patienten, den Anästhesisten und den Behandler. Beide Opioide boten stabile kardiozirkulatorische Verhältnisse. Die opioidinduzierte Atemdepression war sowohl unter Alfentanil als auch unter Sufentanil gleich ausgeprägt. Die Analgesiequalität wurde sowohl vom Patienten als auch vom Anästhesisten gleich gut beurteilt. Während die Vigilanzbeurteilung durch den Anästhesisten keine Unterschiede zeigte, fühlten sich die Patienten bis 2 h nach Behandlungsende signifikant müder unter Sufentanil. Opioidtypische Nebenwirkungen traten unter Sufentanil häufiger auf (24 vs. 11). Diese führten zu einer insgesamt schlechteren Beurteilung des Narkoseverfahrens durch die Patienten und den Anästhesisten. Dies läßt Sufentanil für die intravenöse Analgesie weniger geeignet erscheinen.

Abstract

Extracorporeal shock-wave lithotripsy (ESWL) is the method of choice for the treatment of solitary stones in the kidney or ureter. Early lithotripters required prolonged immobility of the patient and caused considerable pain, necessitating general or epidural anaesthesia during the procedure. Modern lithotripters are quicker, but still require analgesia. Intravenous opioids are currently the drugs in favour. The opioids most commonly used are fentanyl and its shorter-acting analogue, alfentanil. The latter has a more rapid onset and, because of its reduced lipid solubility, is less cumulative. Sufentanil is a new opioid that is also of the phenylpiperidone group and has been recently licensed and introduced in Germany. Its pharmacokinetic and pharmacodynamic properties suggest an intermediate duration of action, high analgesic potency, and cardiovascular stability with diminished respiratory depression. In this prospective double-blind study, the effects of alfentanil and sufentanil on cardiovascular and respiratory parameters, the quality of analgesia, degree of sedation and the number and type of side-effects were compared.

Patients and methods. After giving informed consent and with the approval of the hospital ethics committee, 62 patients (ASA I or II) were investigated. They were randomly allocated to two groups, either receiving sufentanil (n=32) or alfentanil (n=30) during ESWL. No premedication was given. Excluded were patients with pain prior to treatment, patients treated with a spasmolytic or analgesic drug and those who had undergone ESWL within the last 6 months. The loading dose was given as a 5-min infusion to each group. The heart rate, systolic and diastolic blood pressure, percutaneous oxygen saturation (SpO₂), and the transcutaneous capillary carbon dioxide tension (P_tcCO₂) were recorded prior to the procedure (i.e. before administration of opioid), after 1000 and after 2000 shock waves and then 1 and 2 h after the end of lithotripsy. After 1000 and 2000 shock waves, and 1 an 2 h after the treatment, the patients were asked to express their degree of tiredness and pain on a visual analogue scale (VAS). The occurrence of side-effects such as nausea, vomiting, pruritus or other unpleasant sensations were noted by an anaesthesia nurse. Simultaneously, the anaesthetist recorded his/her impression of the patient's tiredness and degree of pain, both by using the VAS. He was not allowed to question the patient, nor was he aware of the patient's own scores. At the end of the observation period both the patient and the anaesthetist related their overall satisfaction with the anaesthetic procedure, again by using the VAS. Data were analysed with the Mann-Whitney-U for comparisons between groups and with the Wilcoxon test within each group. The side-effects were analysed with the Chi-square test.

Results. The systolic and diastolic blood pressure remained stable in both groups during and after treatment. The mean heart rate was different between the two groups at the beginning, and after the end of the treatment it dropped in both groups, but no significant difference was seen between groups. The P_tcCO₂ rose from an initial mean of 36.8 mm Hg to a maximum of 44.6 mm Hg after 1000 shock waves in the sufentanil group, and from 37.8 mm Hg to 46.0 mm Hg after 2000 shock waves in the alfentanil group. The differences were significant within groups until 1 h after the end of the treatment, but there was no significant difference between groups. The oxygen saturation SpO₂ dropped slightly in both groups. The differences were not significant between groups. In the alfentanil group, one patient had a maximum carbon dioxide tension of 83 mm Hg after 2000 shock waves, whereas in the sufentanil treated group the oxygen saturation fell to 72% in one case. Sufentanil-treated patients felt more tired than those who received alfentanil. While the difference in patient's judgement was significant from 2000 shock waves until the end of the observation period, the anaesthetists' assessment showed only a slight trend towards more tiredness after sufentanil. Both opioids provided good analgesia, as judged by both the anaesthesist and the patient, with no differences between groups. The overall satisfaction with the treatment was less with sufentanil than with alfentanil as judged by both the anaesthetist (6.52 vs 7.64) and the patient (7.77 vs 8.86). The adverse effects observed were significantly more frequent in the sufentanil group (24 vs 11). This was mainly due to a higher incidence of itching and nausea. Other side-effects, such as extrapyramidal motor disorders, chest wall and muscular rigidity or disturbed swallowing, were only seen in patients who received sufentanil. Both drugs caused vomiting, motor restlessness and anxiety with the same frequency.

Discussion. Each of the drugs used in this study provided good or excellent pain relief for ESWL with good haemodynamic stability. The increase in carbon dioxide tension and the drop in oxygen saturation in some cases suggest that the routine use of a transcutaneous carbon dioxide analyser and a pulse oximeter to monitor extreme hypercarbia or hypoxaemia is necessary. We did not find less respiratory depression in sufentanil-treated patients, although the maximum measured P_tcCO₂ was not as high as in the alfentanil group. However, this study clearly showed that sufentanil had more of a sedative effect, as perceived by the patient. With the dosage regimens used in this study, there was a higher incidence of side-effects in the sufentanil group without any advantage over alfentanil. It is our opinion that these side-effects lead to both anaesthetists and patients rating alfentanil as better than sufentanil. Perhaps a reduction in the sufentanil maintenance dose would decrease the incidence of side-effects without adversely affecting analgesia. Further studies with a reduced doses of sufentanil are required to answer this question.