J. J. de Lange

The treatment of complex regional pain syndrome type I with free radical scavengers: a randomized controlled study

&NA; To compare the effects of two free radical scavengers, dimethylsulfoxide 50% (DMSO) and N‐acetylcysteine (NAC), for treatment of complex regional pain syndrome I (CRPS I), a randomized, double‐dummy controlled, double‐blind trial was conducted. Two outpatient clinics of two university hospitals in The Netherlands participated in the study and 146 patients, were included over a period of 24 months. Patients were randomized into two treatment groups, one was instructed to apply DMSO 50% five times daily to the affected extremity, the second was treated with NAC 600 mg effervescent tablets three times daily, both combined with placebo. Interventions were accompanied by pain medication, occupational therapy for upper extremity CRPS I and physical therapy for lower extremity CRPS I in specific circumstances. Treatment was given for 17 weeks, with a possibility to continue or switch medication after this period, up to 1 year following the onset of treatment. An impairment level sum score was the primary outcome measure. Upper and lower extremity skills and functions, and general health status were also evaluated. Overall, no significant differences were found between NAC and DMSO after 17 and 52 weeks on impairment level and general health status. Significant differences were found for subscores of lower extremity function, in favor of DMSO‐treatment. Subgroup analysis showed more favorable results for DMSO for warm CRPS I and significantly better performance of NAC for patients with a cold CRPS I. Results tended to be negatively influenced if the duration of the complaint was longer. Treatment with DMSO and NAC are generally equally effective in treatment of CRPS I. Strong indications exist for differences in effects for subgroups of patients with warm or cold CRPS I: for warm CRPS I, DMSO‐treatment appears more favorable, while for cold CRPS I, NAC‐treatment appears to be more effective.

Dosage scheme for propofol in children under 3 years of age

Background : Propofol is a well‐known drug for adults for total intravenous anaesthesia. Since 1999, the use of propofol has been approved for children less than 3 years of age. However, a suitable dosage scheme for these age groups was not available. The purpose of this study was to describe our clinical experience with the use of a new dosage scheme for propofol in patients under 3 years of age, based on experimental data and known pharmacological principles in children.

Effect of sevoflurane on the ex vivo secretion of TNF-α during and after coronary artery bypass surgery

Background and objective: Sevoflurane has been used for the induction and maintenance of anaesthesia during cardiac surgery owing to its favourable haemodynamic effects. It has been suggested that it offers protection against myocardial ischaemia‐reperfusion injury. Methods: We investigated the effect of sevoflurane on plasma concentrations of tumour necrosis factor‐&agr; (TNF‐&agr;) after ex vivo stimulation of whole‐blood leukocytes by lipopolysaccharide from 20 patients undergoing coronary artery bypass surgery. The patients were randomized to two groups. Group 1 patients were induced and maintained with sevoflurane; those in Group 2 were anaesthetized with moderate doses of midazolam‐sufentanil. Blood samples were drawn from the patients on seven occasions from before induction of anaesthesia until 24 h after skin closure. Results: Plasma concentrations of TNF‐&agr; were lower in Group 1 than in Group 2 after cessation of cardiopulmonary bypass (median (interquartiles): 25 (21‐30) versus 37 (28‐79) pg mL−1; P < 0.05) and 24 h after skin closure (196 (100‐355) versus 382 (233‐718) pgmL−1; P < 0.05). Postoperatively, two cases of myocardial infarction were recorded, one in each group. Six patients in Group 2 needed continued inotropic support after the first morning to maintain haemodynamic stability versus one patient in Group 1 (P < 0.05). The length of stay in the intensive care unit was significantly lower in Group 1 than in Group 2 (mean ± SD: 25 ± 16 versus 54 ± 30 h; P < 0.05). Conclusions: Sevoflurane reduces production of TNF‐&agr; more than total intravenous anaesthesia with midazolam‐sufentanil during cardiac surgery. This may reduce cardiac morbidity and the length of stay in the intensive care unit.

Neurohistopathological findings after continuous intrathecal administration of morphine or a morphine/ bupivacaine mixture in cancer pain patients

Background: As the number of terminal cancer patients receiving continuous intrathecalinfusion of opioids and local anesthetics for relief of pain increases, we decided to investigate the post‐mortem findings of the spinal cord, meninges and nerve roots of patients after continuous intrathecal administration of morphine and combined with bupivacaine.

The differential effect of propofol on contractility of isolated myocardial trabeculae of rat and guinea‐pig

The effects of propofol on myocardial contractility were studied in rat, in which the contractile activation mainly depends on calcium derived from the sarcoplasmic reticulum (SR), and guinea‐pig, in which transsarcolemmal influx of calcium plays a major role. Intact and chemically skinned trabeculae from the right ventricle were studied. Intact trabeculae were electrically stimulated and force development during steady state and post rest contractions was measured. In saponin skinned trabeculae Ca2+ uptake and release by the SR was studied. In Triton skinned trabeculae the influence of propofol on calcium sensitivity of the myofilaments was studied. In intact rat trabeculae propofol in concentrations of 28, 112 and 280 μM did not change peak force development nor the pattern of post rest contraction. In guinea‐pig trabeculae propofol significantly reduced peak force to respectively 64, 40 and 23% of control values and the post rest contractions were potentiated. In skinned trabeculae propofol did not affect Ca2+ handling by the SR, nor did it change force production and Ca2+ sensitivity of the myofilaments. This study shows that, in contrast to rat, in guinea‐pig propofol directly depresses myocardial contractility, probably by decreasing transsarcolemmal Ca2+ influx. There is no significant influence of propofol on Ca2+ handling by the SR, nor on the contractile proteins.

Interrater reliability of diagnosing complex regional pain syndrome type I

Background:  Diagnosis of complex regional pain syndrome type I (CRPS I) is based on clinical observation of symptoms. As little information is available on the reliability of CRPS I diagnosis, we evaluated the agreement between therapists with regard to the presence and severity of CRPS I and its symptoms.

Compliance in administration of prescribed analgesics

In this noninterventional study, the implementation of ‘modern’ pain management in clinical practice was investigated by recording the regular prescription, administration and efficacy of analgesic drugs. This resulted in a reproducible and superficial quality control design for hospitals. One hundred and fifty surgical patients were followed during 5 days postoperatively. For every patient, pain, mood and sedation were measured using visual analogue and verbal descriptive scores; the prescription of analgesics at set times and administered doses of analgesics were also recorded. Only paracodeine and naproxen were administered regularly as prescribed, unlike paracetamol and morphine. The prescribed daily dose of morphine was only received by 4.2% of all patients. Although the postoperative pain treatment pathway was considered to be improved after better education and communication, in fact the opposite was found. This is probably caused by traditional thinking, lack of control and time pressure on the hospital staff and the subservient attitude of the patient.

Postoperative condition after the use of remifentanil with a small dose of piritramide compared with a fentanyl-based protocol in patients undergoing craniotomy

Background and objective: The use of remifentanil requires other analgesics for postoperative pain relief compared to fentanyl in patients undergoing craniotomy. This could possibly reduce the postoperative advantages of this short‐acting opioid. Methods: We compared remifentanil and fentanyl‐based anaesthesia in a randomized observer and patient blinded trial on patients, undergoing an elective craniotomy. Twenty patients received anaesthesia using remifentanil with a small dose of piritramide (0.1 mg kg−1) after closure of the dura mater. Twenty patients underwent a fentanyl‐based protocol. In both groups, anaesthesia was induced with thiopental and rocuronium, and maintained with 0.6‐1 minimum alveolar concentration (MAC) isoflurane in a nitrous oxide/oxygen mixture 2: 1 and rocuronium. Patients received 1 g of paracetamol rectally postoperatively. A visual analogue scale (VAS) for pain, the Glasgow Coma Score, a modified Aldrete Score, arterial carbon dioxide tension (PaCO2) and piritramide consumption were evaluated every half an hour postoperatively. Results: No significant differences were found for pain, Aldrete or Glasgow Coma scores or for PaCO2 between the groups when controlled for age, although the pain and Glasgow Coma Scores were consistently higher and PaCO2 lower in the remifentanil group. Furthermore, 13 out of 20 patients in the remifentanil group requested extra piritramide as opposed to 7 out of 20 in the fentanyl group (P = 0.11). Conclusions: Despite the intraoperative use of piritramide in the remifentanil group, patients experienced more pain postoperatively. A significant influence of age on pain intensity was found. The use of remifentanil with a small dose of piritramide of 0.1 mg kg−1 has no evident advantage over the use of fentanyl considering the postoperative conditions after craniotomy.

Sevoflurane-induced cardioprotection is mediated by protein kinase C-alfa via production of reactive oxygen species: 4AP3-6

35 minutes of global ischaemia followed by 60 minutes of reperfusion (I/R). The hearts were randomly divided into 4 groups: (1) control (CON, n 8); (2) sevoflurane preconditioning (SEVO, n 8) receiving three times 5-minute episodes of sevoflurane (2,5 vol%) before I/R; (3) pre-treatment 1 g/ml bupivacaine during 40 minutes before I/R combined with sevoflurane preconditioning (BUPI-SEVO, n 8); and (4) bupivacaine pre-treatment alone (BUPI, n 4). After I/R, cardiac function was determined as recovery of left ventricular pressures (LVP, expressed as percentage to values before I/R) and cellular injury was determined by infarct size with triphenyltetrazolium chloride (TTC) staining. Results: After I/R, the SEVO group showed increased recovery of LVP (53 3% SEVO vs. 46 3% CON, n 8, p 0.05), as well as a reduced infarct size (25 8% SEVO vs. 59 6% CON, n 6, p 0.01). Interestingly, in the BUPI-SEVO and BUPI group infarct size was reduced to a similar extent as the SEVO group (24 7% BUPI-SEVO n 8 and 34 3% BUPI n 4 vs. CON, p 0.05), whereas LVP were unaltered compared to controls. Conclusion: The efficacy of the volatile anaesthetic sevoflurane-induced cardioprotection against ischaemia-reperfusion injury was not affected by the local anaesthetic bupivacaine. Therefore, we suggest that both anaesthetics might induce similar cardioprotective signalling pathways.

THE DIFFERENTIAL EFFECT OF PROPOFOL ON CONTRACTILITY OF ISOLATED MYOCARDIAL TRABECULAE OF RAT AND GUINEA PIG

1. The effects of propofol on myocardial contractility were studied in rat, in which the contractile activation mainly depends on calcium derived from the sarcoplasmic reticulum (SR), and guinea-pig, in which transsarcolemmal influx of calcium plays a major role. 2. Intact and chemically skinned trabeculae from the right ventricle were studied. Intact trabeculae were electrically stimulated and force development during steady state and post rest contractions was measured. In saponin skinned trabeculae Ca(2+) uptake and release by the SR was studied. In Triton skinned trabeculae the influence of propofol on calcium sensitivity of the myofilaments was studied. 3. In intact rat trabeculae propofol in concentrations of 28, 112 and 280 microM did not change peak force development nor the pattern of post rest contraction. In guinea-pig trabeculae propofol significantly reduced peak force to respectively 64, 40 and 23% of control values and the post rest contractions were potentiated. In skinned trabeculae propofol did not affect Ca(2+) handling by the SR, nor did it change force production and Ca(2+) sensitivity of the myofilaments. 4. This study shows that, in contrast to rat, in guinea-pig propofol directly depresses myocardial contractility, probably by decreasing transsarcolemmal Ca(2+) influx. There is no significant influence of propofol on Ca(2+) handling by the SR, nor on the contractile proteins.