Use of a sparse sampling study design to assess transfer of tramadol and its O-desmethyl metabolite into transitional breast milk.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: There are presently no published data on tramadol transfer into breast milk or on its effects in the breastfed infant. WHAT THIS STUDY ADDS: We have provided quantitative data on the absolute and relative infant doses of rac-tramadol and it rac-O-desmethyl metabolite for the breastfed infant. We have also demonstrated a novel sparse sampling data collection method for investigating infant exposure via milk. AIMS: To investigate the transfer of rac-tramadol and its rac-O-desmethyl metabolite into transitional milk, and assess unwanted effects in the breastfed infant. METHODS: Tramadol HCl (100 mg six hourly) was administered to 75 breastfeeding mothers for postoperative analgesia on days 2-4 after Caesarian section. Milk and plasma samples were collected after administration of four or more doses. Rac-tramadol and rac-O-desmethyltramadol were measured by high performance liquid chromatography. Milk : plasma ratio (M : P) and infant doses were calculated by standard methods. The behavioural characteristics of the exposed breastfed infants and a matched control group of infants not exposed to tramadol were also studied. RESULTS At steady-state, mean (95% CI) M : P was 2.2 (2.0, 2.4) for rac-tramadol and 2.8 (2.5, 3.1) for rac-O-desmethyltramadol. The estimated absolute and relative infant doses were 112 (102, 122) microg kg(-1) day(-1) and 30 (28, 32) microg kg(-1) day(-1), and 2.24% (2.04, 2.44)% and 0.64% (0.59, 0.69)% for rac-tramadol and rac-O-desmethyltramadol, respectively. The exposed infants and control breastfed infants had similar characteristics, including Apgar scores at birth and Neurologic and Adaptive Capacity Scores. CONCLUSIONS: The combined relative infant dose of 2.88% at steady-state was low. The similarity of NACS in exposed infants and controls suggests that there were no significant behavioural adverse effects. We conclude that short-term maternal use of tramadol during establishment of lactation is compatible with breastfeeding.

A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.

BACKGROUND: Although pregabalin shows efficacy against neuropathic pain, very limited evidence supports postoperative analgesic efficacy. Our study objective was to investigate analgesic efficacy in an ambulatory day surgical population experiencing acute visceral pain. The null hypothesis was that there was no significant difference in pain relief between pregabalin and placebo. METHODS: A randomized, double-blind, parallel-group, placebo-controlled trial was performed in 90 women having minor gynecological surgery involving the uterus. Patients received either oral pregabalin 100 mg (Group PG) or placebo (Group C) approximately 1 h before surgery. The primary outcome was pain score in the recovery unit and patients were followed for 24 h. RESULTS: There was no significant difference between groups for pain experienced in the recovery room (median, interquartile range 16, 0-36 vs 10, 6.5-36 for Groups PG and C, respectively, P = 0.80) or thereafter; nor for recovery room fentanyl requirement (42% Group PG versus 27% Group C, P = 0.12) or the quality of recovery at 24 h postoperatively (median, interquartile range score 17, 17-18 Group PG versus 18, 16.5-18 Group C, P = 0.75). The incidence of posthospital discharge light-headedness, visual disturbance, and difficulty with walking was significantly higher in the pregabalin group. CONCLUSIONS: A single preoperative dose of 100 mg pregabalin does not reduce acute pain or improve recovery after minor surgery involving only the uterus.

Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labour.

PURPOSE: We compared the efficacy of epidural continual intermittent boluses (CIB) with a continuous epidural infusion (CEI) in prolonging labour analgesia induced by the combined spinal epidural (CSE) technique. METHODS: CSE was instituted in 42 nulliparous parturients at the L3 to 4 level with intrathecal (IT) fentanyl 25 micro g followed by an epidural test dose of 3 mL of 1.5% lidocaine. These parturients were then randomly assigned to receive either epidural CIB (n = 21) or CEI (n = 21) with 0.1% ropivacaine and fentanyl 2 micro g x mL(-1). For the CIB, 5 mL boluses were given hourly, with the first bolus 30 min postinduction. CEI at the rate of 5 mL.hr(-1) was initiated in the minute after CSE. The duration of analgesia, pain score, degree of sensorimotor block were compared. RESULTS: From Kaplan Meier survival analysis, the duration of analgesia was significantly longer in CIB (mean survival time 239 +/- SD 24 min vs 181 +/- 17, P < 0.05 using log rank test). During the first three hours postblock, the median sensory block to cold was higher in CIB (P < 0.05, Mann U Whitney test) but no difference in blood pressure was detected [P > 0.05, repeated measure analysis of variance (RMANOVA)]. The serial pain scores were lower in the CIB (P < 0.05, RMANOVA). CONCLUSION: CIB prolonged the duration and improved the quality of analgesia. CIB could have resulted in an improved spread of analgesics in the epidural space or encouraged a direct passage of infusate into the IT space. This could have also rendered a higher sensory block to cold in the CIB group. CIB is a good alternative to CEI for the maintenance of epidural analgesia after CSE.