Alex T. Sia

A118G single nucleotide polymorphism of human μ-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia

Background:Previous studies have shown that genetic variability at position 118 of the human &mgr;-opioid receptor gene altered patients’ response to intravenous morphine. The purpose of this study was to investigate whether this polymorphism contributes to the variability in response to morphine for postcesarean analgesia. Methods:After investigators obtained informed consent, 588 healthy women received 0.1 mg intrathecal morphine for postcesarean analgesia. Their blood samples were genotyped for the A118G polymorphism—A118 homozygous (AA), heterozygous (AG), or homozygous for the G allele (GG). Pain scores, the severity of nausea and vomiting, the incidence of pruritus, and the total self-administered intravenous morphine were recorded for the first 24 postoperative hours. Results:Two hundred seventy women (46%) were AA, 234 (40%) were AG, and 82 (14%) were GG. The 24-h self-administered intravenous morphine consumption was lowest in the AA group (P = 0.001; mean, 5.9; 95% confidence interval, 5.1–6.8) versus the AG (8.0; 6.9–9.1) and GG groups (9.4; 7.3–11.5). Pain scores were lowest in the AA group and highest in the GG group, with a statistically significant difference detected between AA, AG, and GG (P = 0.049). Total morphine consumption was also influenced by patients’ age and paying status. AA group was associated with the highest incidence of nausea (26 of 272 [9.6%]; P = 0.02) versus the other two groups (13 of 234 [5.6%] and 1 of 82 [1.2%] for AG and GG, respectively). Conclusion:Genetic variation at position 118 of the &mgr;-opioid receptor is associated with interindividual differences in pain scores, self-administered intravenous morphine, and the incidence of nausea postoperatively.

Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain

BackgroundMorphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery.ResultsData on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 × 10-5) and weight-adjusted morphine (p = 6.6 × 10-5). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class.ConclusionOur results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.

Ethnic differences in pain perception and patient-controlled analgesia usage for postoperative pain.

UNLABELLED There are reports suggesting that sensitivity to and tolerance of both clinical and experimental pain differ among ethnic groups. We examined self-rated pain score and morphine usage in 1034 women who underwent elective lower cesarian section (LSCS) for their deliveries. Data on pain scores and amount of total morphine use according to patient-controlled analgesia were collected every 4 hours. Overall, lowest pain scores were recorded 12 hours after surgery and highest at 24 hours. Morphine consumption was highest within the first 4 hours and lowest between 12 and 16 hours. There were statistically significant ethnic group differences in pain scores (P = 1.7 x 10(-7)) and morphine usage (P = 2.8 x 10(-15)) between ethnic groups, with Indians having the highest mean pain score and using the highest amount of morphine. The ethnic differences in pain score and morphine self-administration persisted after controlling for age, body mass index, and duration of operation. PERSPECTIVE Our findings of highly significant ethnic group difference in self-reported pain level and the amount of analgesia self-administered may have implications on optimal management of acute postoperative pain. Inadequate management of pain after cesarian deliveries might affect the emotional well-being and physical recovery of patients and affect mother-child bonding.

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

PurposeWe 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.MethodsCSE was instituted in 42 nulliparous parturients at the L3 to 4 level with intrathecal (IT) fentanyl 25 μg 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 μg·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.ResultsFrom 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).ConclusionCIB 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.RésuméObjectifComparer l’efficacité de bolus périduraux intermittents administrés en continu (BIC) avec la perfusion péridurale continue (PPC) comme analgésie prolongée pendant le travail induite selon une technique rachidienne péridurale combinée (RPC).MéthodeL’analgésie RPC a été installée chez 42 parturientes nullipares au niveau L3 à 4 avec 25 μg de fentanyl intrathécal (IT) suivi d’une dose test péridurale de 3 mL de lidocaïne à 1,5 %. Les patientes ont été randomisées pour recevoir soit des BIC périduraux (n = 21), soit une PPC (n = 21) avec ropivacaïne à 0,1 % et 2 μg·mL−1 de fentanyl. Dans le cas des BIC, des bolus de 5 mLà chaque heure ont été donnés, dont le premier 30 min après l’induction. La PPC a débuté une minute après la RPC à raison de 5 mL·h−1. La durée de l’analgésie, les scores de douleur, le degré de bloc sensorimoteur ont été comparés.RésultatsÀ partir de l’analyse de survie de Kaplan Meier, on a trouvé une analgésie significativement plus longue avec les BIC (temps de survie moyen de 239 ± l’écart type 24 min vs 181 ± 17, P < 0,05 avec le test du logrank). Pendant les trois premières heures suivant le bloc, le bloc sensitif moyen au froid a été plus élevé avec les BIC (P < 0,05, test U de Mann Whitney) mais aucune différence de tension artérielle n’a été détectée [P > 0,05, analyse répétée de la variance à plusieurs variables (repeated measure analysis of variance RMANOVA)]. Les scores de douleur en série ont été plus bas avec les BIC (P < 0,05, RMANOVA).ConclusionLes BIC ont prolongé la durée et amélioré la qualité de l’analgésie. Les BIC peuvent améliorer la diffusion de l’analgésie dans l’espace péridural ou favoriser le passage direct de la perfusion dans l’espace IT. Cette technique peut aussi avoir augmenté le bloc sensitif au froid. Les BIC sont un bon équivalent de la PPC pour le maintien de l’analgésie péridurale après la RPC.

A comparison of a basal infusion with automated mandatory boluses in parturient-controlled epidural analgesia during labor.

BACKGROUND:The use of parturient-controlled epidural analgesia (PCEA) with a basal infusion is commonly used in laboring women. We compared a novel approach of providing basal intermittent boluses concurrently with PCEA: PCEA plus automated mandatory boluses (PCEA+AMB) versus PCEA plus basal continuous infusion (PCEA+BCI). We hypothesized that epidural local anesthetic consumption would be lower if basal intermittent boluses were used instead of a basal infusion. METHODS:We randomized 42 healthy parturients in early labor to receive 0.1% ropivacaine + fentanyl 2 &mgr;g/mL either via PCEA+BCI (n = 21,bolus 5 mL, lockout 10 min, basal infusion 5 mL/h) or via PCEA+AMB (n = 21, patient-activated bolus of 5 mL, lockout 10 min, basal automated boluses of 5 mL/h [omitted if a patient-activated bolus was successfully administered in the last 1 h]) after successful induction of combined spinal epidural analgesia. RESULTS:We found a reduction in the hourly consumption of ropivacaine with PCEA+AMB, i.e., the primary outcome measure (mean = 6.5 mL, sd = 3.4 in the PCEA+AMB group vs 7.5 mL, sd = 2.0 PCEA+BCI group, P = 0.011). A larger proportion of parturients in the PCEA+AMB group did not self-bolus (6/21 vs 1/21 in PCEA+BCI, P = 0.03). The time to the first self-bolus after combined spinal epidural was longer in the PCEA+AMB group (mean survival time 315 min vs 190 min in PCEA+BCI group, P = 0.04 by log rank test). There was no difference in pain scores or side effects. CONCLUSION:Our study showed that PCEA+AMB reduced analgesic consumption and could be useful as the mode of maintenance for epidural analgesia.

Colloid Preload Versus Coload for Spinal Anesthesia for Cesarean Delivery : The Effects on Maternal Cardiac Output

BACKGROUND: Spinal anesthesia for cesarean delivery may cause severe maternal hypotension, and a decrease in cardiac output (CO) and blood flow to the placenta. Fluid preloading with crystalloid is ineffective due to rapid redistribution. A “coload” given at the time of cerebrospinal fluid identification may be more effective. Our null hypothesis was that there would be no difference between the effect of a colloid preload (15 mL/kg hydroxyethyl starch (HES) 130/0.4 [Voluven® 6%]) and an identical coload on maternal CO and the incidence of hypotension after spinal anesthesia for cesarean delivery. Secondary outcomes studied were neonatal acid- base status and predelivery vasopressor requirements. METHODS: Forty ASA PS I and II women scheduled for elective cesarean delivery were recruited. Patients were randomized to Group P (preload of 15 mL/kg HES) or Group C (coload, given when cerebrospinal fluid identified). Heart rate, arterial blood pressure, stroke volume and CO measurements were recorded at baseline, every minute for 10 min, and every 2.5 min interval for 10 min with the USCOM™ ultrasonic CO monitor. Spinal anesthesia was performed at the L3/4 interspace in the right lateral position. Arterial blood pressure was maintained at 90%–100% of baseline values using IV phenylephrine boluses. RESULTS: Demographic, anesthetic, and surgical characteristics were similar. There were no between-group differences in baseline systolic blood pressure, heart rate, and colloid volume. CO and stroke volume were significantly increased in Group P (P = 0.01) in the 5 min after spinal anesthesia. This increase in CO was not sustained at 10 min. There were no significant between-group differences in the incidence of hypotension, absolute arterial blood pressure values (P = 0.73), predelivery median (range) phenylephrine requirements (300[0–1000] in Group P versus 150 [0–850]&mgr;g in Group C, P = 0.24), or neonatal outcome as measured by Apgar scores and umbilical arterial and venous blood gas values. CONCLUSION: Intravascular volume expansion with 15 mL/kg HES 130/0.4 given as a preload, but not coload, significantly increased maternal CO for the first 5 min after spinal anesthesia for cesarean delivery, however, maternal and neonatal outcomes were not different.

Combined spinal epidural causes higher level of block than equivalent single-shot spinal anesthesia in elective cesarean patients

Combined spinal epidural (CSE) is an established technique for lower segment cesarean delivery. In this study we tested the hypothesis that the spinal block from a CSE technique results in a more extensive spread of local anesthetic in the subarachnoid space than the single-shot spinal (SSS) technique. We recruited 30 ASA physical status I parturients admitted for elective lower segment cesarean delivery into our randomized, controlled, double-blind study. All patients intrathecally received 2 mL of 0.5% hyperbaric bupivacaine. The patients were randomized into one of the two groups using sealed opaque envelopes. Group S (n = 15) received a SSS technique. Group CS (n = 15) received a CSE technique using loss of resistance to 2 mL of air, but the epidural catheter was not inserted after the intrathecal drug administration. The maximal sensory block achieved in group CS was statistically higher than that in Group S (median C6 interquartile range, C5 to C8 versus median T3, T2 to T4, P < 0.001). Time taken to reach maximal sensory block was significantly longer in group CS. There were no differences in the time taken for the block to recede to T10, hemodynamic profile, or side effects. In conclusion, the CSE technique without placing an epidural catheter or administering epidural medication resulted in a significantly higher level of sensory block when compared with the SSS technique when the same dose of local anesthetic was given intrathecally.

A randomised trial of the analgesic efficacy of ultrasound-guided transversus abdominis plane block after caesarean delivery under general anaesthesia.

Context Previous studies examining the efficacy of transversus abdominis plane block after caesarean section have mostly been in parturients under spinal anaesthesia. Objectives We postulated that the advantage of performing transversus abdominis plane block after caesarean section might be even more obvious after general anaesthesia, resulting in reduced 24-h consumption of morphine. Design, setting, patients and interventions In this single centre, randomised double-blind controlled trial, 40 women who underwent caesarean delivery under general anaesthesia were allocated randomly to receive a transversus abdominis plane block or no block. In those who received the block, 20 ml of levobupivacaine 2.5 mg ml−1 was deposited bilaterally into the transversus abdominis plane under ultrasound guidance using a Sonosite Titan (SonoSite, Bothell, Washington, USA) 7–13 MHz linear transducer at the end of surgery when the patient was still anaesthetised. Main outcome measures We recorded patient-controlled intravenous morphine use for 24 h, pain scores at rest and activity, sedation, nausea and vomiting, use of antiemetic medication and overall maternal satisfaction. The primary outcome was 24-h morphine consumption. Results Patients who received the transversus abdominis plane block used significantly less morphine in 24 h than those in the control group [12.3 (2.6) vs. 31.4 mg (3.1), P < 0.001) and had higher satisfaction scores [16 (80%) vs. 5 (25%), P = 0.012). There were no differences between groups in the visual analogue pain scores, sedation level, nausea and vomiting or the use of antiemetic medication. Conclusion Ultrasound-guided transversus abdominis plane block reduced morphine consumption following caesarean section under general anaesthesia, with increased maternal satisfaction.

Failure of augmentation of labor epidural analgesia for intrapartum cesarean delivery: a retrospective review.

In this study, we aimed to identify the incidence and predictive factors associated with failed labor epidural augmentation for cesarean delivery. Data of parturients, who had received neuraxial labor analgesia and who subsequently required intrapartum cesarean delivery during an 18-mo period, were retrospectively studied. Predictors associated with failure of extension of epidural analgesia in the presence of adequate time for onset of epidural anesthesia were identified by univariate logistic regression. Of the 1025 parturients, 1.7% had failed epidural extension. Predictors of failed epidural anesthesia included initiation of labor analgesia with plain epidural technique (compared to combined spinal-epidural) (P = 0.001), ≥2 episodes of breakthrough pain during labor (P < 0.001) and prolonged duration of neuraxial labor analgesia (P = 0.02).

A randomized controlled trial of three patient-controlled epidural analgesia regimens for labor.

BACKGROUND:Patient-controlled epidural analgesia (PCEA) is a safe and effective mode of maintaining labor analgesia; however, the ideal PCEA regimen is controversial. METHODS:In this prospective, randomized, double-blind study, we examined the analgesic efficacy of demand-only PCEA and PCEA with background infusion. We recruited 300 nulliparous parturients. Analgesia was initiated with intrathecal ropivacaine 2 mg and fentanyl 15 μg and maintained with epidural ropivacaine 0.1% with fentanyl 2 μg/mL. Parturients were randomized to one of three groups. Group 0: demand-only PCEA, bolus of 5 mL, lockout interval of 15 min. Group 5: background infusion of 5 mL/h, bolus of 5 mL, lockout interval of 12 min. Group 10: background infusion of 10 mL/h, bolus of 5 mL, lockout interval of 10 min. The maximum dose of all groups was 20 mL/h. The primary outcome was incidence of breakthrough pain. Secondary outcomes included intrapartum pain scores, neuraxial blockade characteristics, side effects, the total and hourly volume of ropivacaine, neonatal outcomes, and obstetric outcomes. RESULTS:The incidence of breakthrough pain and the maximum visual analog scale (0–100 mm scale) pain scores were higher in Group 0 versus Groups 5 and 10 (43% vs 17% and 11%, P < 0.001 and 37 ± 28 vs 22 ± 26 and 16 ± 25 [mean ± sd], P < 0.001), respectively. Group 10 had a longer duration of effective analgesia compared with Group 0 (mean 895 min, 95% CI 823–966 vs 565 min, 95% CI 454–677, P < 0.001) and increased ropivacaine consumption, and was associated with a longer duration of the second stage of labor. CONCLUSION:Demand-only PCEA (5-mL bolus, 15-min lockout interval) resulted in less local anesthetic consumption but an increased incidence of breakthrough pain, higher pain scores, shorter duration of effective analgesia, and lower maternal satisfaction, when compared with PCEA with background infusion (5-mL bolus, 10–12-min lockout interval, and 5–10 mL/h infusion).