Expert panel consensus recommendations for the pharmacological treatment of acute pain in the Middle East region.

The findings of an expert panel convened to review critically how best to apply evidence-based guidelines for the treatment of acute pain in the Middle East region are presented. The panel recommended a three-step treatment protocol. Patients with mild-to-moderate levels of acute pain should be treated with paracetamol (step 1). If analgesia is insufficient after 1-2 days, a selective cyclo-oxygenase-2 inhibitor or, if gastrointestinal safety and bleeding risk are not an issue, a non-specific nonsteroidal anti-inflammatory drug, should be used (step 2). If analgesia remains inadequate, treatment with tramadol, or paracetamol plus codeine/tramadol is recommended (step 3). Patients reporting severe pain should be referred to a pain clinic or specialist for opioid analgesic treatment. Measures of pain and functioning that have been validated in Arabic, with culturally appropriate and easy to understand descriptors, should be used. Early and aggressive acute pain management is important to reduce the risk of pain becoming chronic, especially in the presence of neuropathic features.

High incidence of post-transplant diabetes mellitus in Kuwait.

Post-transplant diabetes mellitus (PTDM) has been reported to occur in 5-15% of non-diabetic renal transplant recipients. During a 15-year period (January 1983-January 1998), 631 renal transplant recipients (TxR) were followed-up in our Centre of whom 79 (12.5%) had pre-transplant diabetes mellitus. Among the 552 TxR who were non-diabetic at pre-transplantation, 117 (21.2%) developed PTDM. The gender, native renal disease and the mode of pre-transplant dialysis did not differ in those with and without PTDM. Of the 117 TxR who developed PTDM, 63 (53.8%) were above the age of 45 years where as only 90 (20.7%) of the 435 who remained non-diabetic (NDM) were above this age (P<0.05). PTDM occurred in 115 (29.6%) recipients of Arab origin (Kuwaitis and non-Kuwaitis) where as only two (1.7%) non-Arabs developed it. There was no difference in the incidence of PTDM when prednisone and azathioprine (two drug regime) were used or with cyclosporine (triple drug regime). The incidence of acute rejection episodes did not differ among PTDM and NDM groups. The over all incidence of infections requiring hospitalisation was higher in PTDM group (1.8 episodes per patient) compared to NDM group (one episode per patient) during the study period (P<0.001). Coronary heart disease was also more frequent in PTDM (15 vs. 6%, P<0.05). The cumulative graft survival at 1, 5, 10 and 14 years in the PTDM (97, 92, 74 and 67%, respectively) and NDM groups (97, 91, 80 and 73%, respectively) was similar. However, an important cause of graft loss was death of the recipient in PTDM compared to NDM (10.7 vs. 3.6%). Similarly, the patient survival up to 14 years did not differ between PTDM and NDM groups (80 and 82%, respectively), although infection related deaths were more frequent in the PTDM group (65 vs. 49%) although not statistically significant. In conclusion, there is a high incidence of PTDM in Kuwait; age and race being the two important contributory factors. The overall patient and graft survival are not adversely affected by PTDM although infections and coronary heart disease are more frequently encountered in this group.

Cyclosporine neoral: a local experience.

Cyclosporine (CsA) is an effective immunosuppressant drug. Recently a new oral formulation, Sandimune Neoral (SIM-NOF) has been developed to overcome the problems of poor bioavailability, unpredictable blood levels and variable gastro-intestinal absorption seen with the use of traditional Cyclosporine, Sandimune (SIM). We conducted a prospective, open label crossover tolerability, efficacy and safety of SIM-NOF and (2) to compare SIM-NOF with SIM for their bioavailability, absorption pattern and consistence of 12-hour trough levels. Fourteen renal transplant recipients, with stable renal function (serum creatinine stable for more than six immediate previous months) and SIM dosages, were randomly selected for the study. Their age mean +/- SD 38.2+/- 11.1 years, ad had completed 3.8+/- 2.2 years after transplantation. All patients were on triple drug immunosuppression with prednisone, azathioprine and SIM. The study consisted of an initial 12-week period, where SIM was used and cyclosporine 12-hour trough levels were monitored t least every four weeks. This was followed by a run-in period of two weeks, where a 12-hour cyclosporine profiling was done while patients were on SIM. This was followed by a 12-week period, Where SIM-NOF replaced SIM on a 1:1 dose conversion ratio. During this latter period, 12-hour trough levels (at 1,2,3,8 and 12 weeks) were measured. The doses of the SIM-NOF were adjusted to maintain blood cyclosporine trough levels at 50-180 mug/ml. On cyclosporine profiling, SIN-NOF showed a predictable and constant absorption profile peaking at two hours in all instances with steady declining levels through the following ten hours. With SIM the levels were unpredictable and erratic. The Tmax for SIM-NOF was 2.0+/- 0 hours and for SIM 3.7+/- 1.7 hours (p< 0.0001). The Cmax for SIM- NOF was 2149 and for SIM 1942 (p=0.008). The 12-hour trough studies for SIM-NOF is a superior preparation to SIM in clinical practice. No specific adverse effects were observed.

Safety and efficacy of epinephrine added to bupivacaine for lumbar epidural analgesia in obstetrics.

The effects of epidural bupivacaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid-base status, and Neurologic and Adaptive Capacity Scoring System (NACS) were compared in 32 parturients during labor and delivery. Patients in group I (n = 16) received 0.5% bupivacaine with 1:300,000 epinephrine and those in group II (n = 16) received 0.5% bupivacaine alone. Addition of epinephrine to bupivacaine had no significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate and variability, or the incidence of abnormal fetal heart rate patterns. Maternal hypotension occurred less frequently in group I than in group II patients (P less than 0.05). Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I than in group II (186.8 +/- 11.6 vs 85.3 +/- 6.1 (mean +/- SEM) min, P less than 0.001). It is concluded that adding epinephrine to bupivacaine during epidural anesthesia in the normal parturient has no adverse effects on either mother, fetus, neonate, or the progress of labor; and that it significantly prolongs the duration of anesthesia and decreases the incidence of maternal hypotension.

Maternal, fetal, and neonatal effects of lidocaine with and without epinephrine for epidural anesthesia in obstetrics.

The effects of epidural lidocaine with and without 1:300,000 epinephrine on uterine activity, progress of labor, fetal heart rate, maternal blood pressure and heart rate, newborn Apgar scores, neonatal acid-base status, and the Neurologic and Adaptive Capacity Scoring System were compared in 30 parturients during labor and delivery. Patients in group I (n = 16) received 1.5% lidocaine with 1:300,000 epinephrine and those in group II (n = 14) 1.5% lidocaine alone. Addition of epinephrine to lidocaine did not have any significant effects on uterine activity, duration of first or second stages of labor, fetal heart rate variability, or the incidence of abnormal fetal heart rate patterns. Maternal heart rate and the incidence of hypotensive episodes did not differ significantly between the two groups of patients. Apgar scores, neonatal acid-base status, and the NACS were equally good in the two groups. Duration of analgesia was significantly longer in group I as compared to group II patients (106.9 +/- 6.6 vs 66.2 +/- 4.4 min, P less than 0.001). Umbilical venous concentrations of lidocaine and umbilical vein to maternal vein ratios of lidocaine were significantly higher in group II patients (P less than 0.05). It is concluded that addition of epinephrine to lidocaine during epidural anesthesia in the normal parturient has no adverse effects on mother, fetus, neonate, or the progress of labor and it significantly prolongs the duration of anesthesia and limits the placental transfer of lidocaine.