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The article “A Review of Systemic Opioids Commonly Used for Labor Pain Relief” that was published in the May/June 2011 issue of the Journal (2011;56:222–239) contained errors in Tables 2, 3, and 4. In Table 2 (page 225), the data for Active metabolite of morphine: M6G should be separate from that of Morphine and consist of a peak effect at 45 minutes, an adult elimination half-life of 2–4h, neonate elimination half-life of 13.9h, and the comment, “Metabolite produces greater analgesic effect than morphine; can accumulate with repeated doses.” Also in Table 2 (page 225), the data for Active metabolite of meperidine: normeperidine should be separate from that of Meperidine or pethidine (Demerol) and consist of a maternal elimination half-life of 21h, neonate elimination half-life of 63h, and the comment, “Normeperidine accumulates in maternal plasma after multiple doses and affects newborn neuroadaptive scores and breastfeeding behaviors.” In Table 3 (pages 229–231) and Table 4 (pages 233–234), the Study Design and Participants information has now been distinguished and clarified. In Table 3 (page 230), the reference number for Rayburn et al should be 51. In Table 4 (page 234), the second paragraph for Douma et al under the Interventions heading should read, “Control: PCA meperidine 49.5 mg loading dose, 5 mg bolus, 10 min lockout interval, total dose limit 200 mg, or PCA fentanyl (Sublimaze) 50 mcg loading dose, 20 mcg bolus, 5 min lockout interval, maximum dose limit 240 mcg/h.” The correct versions of the tables are as follows:

Table 2.  Pharmacokinetic Profiles of Selected Opioids
Drug(Brand name)Usual DoseOnset(Minutes)Peak Effects(Minutes)Duration ofActionEliminationHalf-lifeComments
  1. Abbreviations: FHR, fetal heart rate; IM, intramuscular; IV, intravenous; M6G, morphine-6-glucuronide; PCA, patient-controlled analgesia.

  2. aACOG75

  3. bBaumann76

  4. cGerdin et al23

  5. dKart et al25

  6. eGustein et al69

  7. fHinova et al64

Morphine Active metabolite of morphine: M6GIV: 2-5 mg/4 ha IM: 10 mg/4 haIV: 5a IM: 10-20bIV: 20 IM: 0.5-1b 45dIV: 1-3 h IM: 3-5 hbAdults: 2 hb Maternal: 43 minc Neonates: 6.5 ± 2.8 hd Adults: 2-4 h Neonates: 13.9 hdFaster absorption when administered in deltoid muscle compared with gluteal muscle Use lower doses with patients with impaired ventilation or asthma Metabolite produces greater analgesic effect than morphine; can accumulate with repeated doses
Meperidine or pethidine (Demerol) Active metabolite of meperidine: normeperidineIV: 25-50 mg/1-2 ha IM: 50-100 mg/2-4 haIV: 5a IM: 10-20bIV: 5 IM: 30-60bIM, IV: 2-4 h IM: 2-5bMaternal: 3-7 h Neonates: 18-23 h Maternal: 21 h Neonates: 63 hFetal exposure highest 1-4 h after maternal administration, with associated neonatal respiratory depression; highest 2-3 h after administration May temporarily decrease FHR variability Normeperidine accumulates in maternal plasma after multiple doses and affects newborn neuroadaptive scores and breastfeeding behaviors
Fentanyl (Sublimaze)IV: 50-100 mcg/ha IM: 50-100 mcg/haIV: 1a IM: 7-15bIV: 5b IM: 10-20bIV: 30-60 min IM: 1-2 hbAdults: 3-4 ha Neonates: 75-440 minWhen administered as an infusion, context sensitive decrement time (the time to a 50% reduction in blood concentration after cessation of a steady infusion) increases; With higher doses or prolonged infusions, fentanyl becomes longer actinge Transient decreased FHR variability Maximum cumulative labor dose is usually 500-600 mcg
Remifentanil (Ultiva)PCA administration with varying dosing0.5–1f2f20 minfAdults: 9 minfPotent maternal respiratory depressant Dose at beginning of uterine contraction
Butorphanol (Stadol)IV: 1-2 mg q 3-4 ha IM: 1-2 mg q 3-4 haIV: 2-3 IM: 10-20bIV: 5-10 IM: 30-60bIV or IM: 4-6 hbAdults: 2.5-3.5 hbMaternal ceiling effect on respiratory depression and analgesia Fetal transient pseudosinusoidal FHR pattern May precipitate acute withdrawal syndrome in an opiate-dependent mother and neonate
Nalbuphine (Nubain)IV or IM: 10 mg/3 haIV: 2-3a IM: <15bIV: 30 IM: 30-60bIV: 2-4 h IM: 4-6 hbAdults: 2-5 hbMaternal ceiling effect on respiratory depression and analgesia at 30 mg May precipitate acute withdrawal syndrome in an opiate-dependent mother and neonate
Table 3.  Summary of Comparative Investigations of Fentanyl (Sublimaze) for Labor Pain Relief
Authors of StudyStudy DesignParticipantsInterventionsOutcomes
  1. Abbreviations: FHR, fetal heart rate; IV, intravenous; PCA, patient-controlled analgesia; SpO2, oxygen saturation with pulse oximetry; VAS, visual analogue scale.

Rayburn et al45Prospective nonrandomized controlled trial 137 parturients in active laborExperimental: IV bolus of fentanyl 50-100 mcg/h. Mean (SD) cumulative fentanyl dose 140 mcg/h (42 mcg) ranging 50-600 mcg. Two-thirds of group received ≤ 100 mcg total dose, and 90% received < 300 mcg. Control: No analgesia or anesthesiaMaternal: Fentanyl group with temporary analgesia, mild sedation, mood modification, temporary relief of fears, relaxation, drowsiness. Fetal: 30 min of decreased variability. Labor: Fentanyl group had higher rate of oxytocin augmentation (P < .0001) and longer active phase labors (P < .001). No difference in route of birth. Newborn: No differences in frequencies of newborn depressed respirations, low Apgar scores, or neurologic and adaptive capacity scoring at 2-4 h and 24 h following birth.
Rayburn et al33Prospective randomized controlled trial 105 parturients in active laborExperimental: IV bolus of fentanyl 50-100 mcg/h Control: IV bolus of meperidine (Demerol) 25-50 mg/hMaternal: VAS pain scores were not significantly different between groups. Pain scores improved only slightly between 8-10 cm and more so at 4-7 cm cervical dilation. Nausea, vomiting, and prolonged sedation less common in the women in the fentanyl group (P < .05). Fetal: FHR variability not statistically different between groups. Labor: No significant differences in duration of labor, oxytocin use, cesarean birth. Newborn: Significantly fewer neonates required naloxone in the fentanyl group (2% vs 13%; P < .05). No difference in Apgar scores, umbilical artery pH, or neurologic and adaptive capacity scoring at 2-4 h and 24 h postnatally.
Atkinson et al50Prospective randomized double-blind, controlled trial 100 parturients in active laborExperimental: IV bolus of fentanyl 50-100 mcg/h, limit 5 doses. Control: IV bolus of butorphanol (Stadol) 1-2 mg every 1-2 h, limit 5 dosesMaternal: Significantly greater reduction in VAS pain scores at 15 and 60 min following initial dose of butorphanol (P < 0.05) compared with fentanyl. At 7-9 cm cervical dilation, pain scores increased and both drugs reduced pain scores only slightly at 15 min after dosing. Mothers in fentanyl group requested more doses (P < .05) and had more requests for epidural (P < .05). Rates of nausea, vomiting, prolonged sedation, and decreased respiratory rate were similar. Fetal: No difference in temporary decrease in FHR variability and pseudosinusoidal pattern. Labor: No difference in contraction frequency or duration, oxytocin augmentation, or cesarean birth. Newborn: No difference in Apgar scores, cord gas values, naloxone use, or neuroadaptive scoring.
Rayburn et al51Prospective randomized controlled trial 80 parturients in active laborExperimental: PCA fentanyl 50 mcg loading dose, 10 mcg/h baseline, 10 mcg demand dose; lockout interval 12 min Maximum hourly dose 60 mcg Cumulative dose used: 149.0 mcg (62.2 mcg), range 70-305 mcg Control: IV bolus of fentanyl 50 mcg loading dose, then 50-100 mcg/h Cumulative dose used: 161.6 mcg (109.2 mcg), range 50-500 mcgMaternal: No difference in pain scores, sedation scores. Fetal: No difference in persistent decreased FHR variability. Labor: No difference in duration of labor. Newborn: No difference in Apgar score, naloxone therapy, or neurologic and adaptive capacity scoring at 24 h.
Nikkola et al52Randomized controlled trial 20 parturients in active laborExperimental: IV PCA fentanyl Loading dose 50 mcg fentanyl, 20 mcg demand dose; lockout interval 5 min; maximum dose 240 mcg/h Cumulative dose range 190 and 885 mcg, mean 447 (202 mcg) Control: epidural (bupivacaine 0.5%)Maternal: Epidural provided significantly better pain relief (P= .01) per VAS pain score. Six of 10 mothers rated effectiveness of fentanyl as good to excellent; 8 of 10 rated epidural effectiveness as good to excellent. Satisfaction with analgesia did not differ significantly between groups. Mothers in fentanyl group had significantly more tiredness and dizziness (P= .001). No difference in rates of nausea and vomiting. Fetal: No difference in FHR variability 1 h after medication. Labor: No difference in labor duration. Newborn: No difference in Apgar scores, umbilical pH, or neurologic and adaptive capacity scoring at 1 and 13 h. During the first 12 h of life, minimum and maximum SpO2 values were significantly lower in the infants in the fentanyl group. SpO2 < 90% was more common with fentanyl group (P= < .001); no infants required O2. Episodes of desaturation < 80% did not differ between groups. No neonates required naloxone.
Halpern et al53Prospective randomized controlled trial 242 parturients in active labor and second stage laborExperimental: Patient controlled epidural (0.08% bupivacaine and fentanyl 1.6 mcg/mL) Mean cumulative epidural fentanyl dose 200 mcg (range 132-244 mcg) Control: IV PCA fentanyl. Loading dose 100 mcg, then 50 mcg as needed until adequate pain relief. Followed by 25-50 mcg PCA demand dose; lockout interval 10 min. Lockout and demand dose could be increased or decreased by anesthesiologist. Total dose used: mean cumulative dose of 940 mcg (range 350-1625 mcg)Maternal: Epidural group with significantly greater reductions in VAS pain scores (P < .001) and higher satisfaction scores (P= .02). Also, less antiemetic therapy (P= .01) and lower sedation scores (P < .001). Fetal: Not evaluated. Labor: Epidural was associated with significantly longer second stage labor (P= .02). No difference in incidence of maternal fever, spontaneous vaginal births, assisted vaginal births, or cesarean births. Newborn: No difference in 5-min Apgar scores, umbilical artery gas values, or neonatal fever. More neonates in fentanyl group required active resuscitation (P= .001), naloxone (17% vs 3%; P= .001), and had lower 1-min Apgar scores.
Table 4.  Randomized Controlled Trials Comparing Remifentanil (Ultiva) to Other Opioids
AuthorStudy DesignParticipantsInterventionsOutcomes
  1. Abbreviations: FHR, fetal heart rate; IM, intramuscular; NS, not significant; PCA, patient-controlled analgesia; VAS, visual analogue scale.

Blair et al41Double-blind, randomized controlled trial 39 parturients during first and second stage laborExperimental: PCA remifentanil 40 mcg/dose, 2 min lockout interval Total doses not reported. Control: PCA meperidine (Demerol) 15 mg/dose, 10 min lockout interval Total doses not available Nitrous oxide option available to both groupsMaternal: No difference between groups in reduction of VAS pain scores during 2 h observation. Overall maternal satisfaction higher (P= .001) with remifentanil. No difference between groups in nausea, anxiety, or maternal desaturation less than 94% or 90%. Sedation increased over time and was similar between groups. Fetal: No change in FHR baseline with both groups. Labor: No difference between groups in labor duration. Newborn: Neurologic and adaptive capacity scores higher (P= .003) with remifentanil at 30 min but similar at 2 h after birth. No difference in Apgar scores or cord pH. Naloxone was not used in either group.
Evron et al63Double-blind, randomized controlled trial 88 parturients, labor stage not reportedExperimental: Increasing doses of PCA remifentanil, 0.27-0.93 mcg/kg/bolus, maximum 1500 mcg/h. Mean total dose/h 270 mcg/kg Control: Intravenous infusion meperidine 75 mg over 30 min. With insufficient analgesia, another 75 mg administered. Additional 50 mg as needed. Maximum dose 200 mg (range 75-200 mg). Mean total dose 150 mgMaternal: Remifentanil associated with lower (P < .001) VAS pain scores at 1 h after initiation of medication and end of first stage labor and higher (P < .001) patient satisfaction scores 24 h after birth. Remifentanil also associated with less (P < .001) sedative effect, fewer (P < .007) desaturation events <95%, and less nausea and vomiting (P < .001) Fetal: Less frequent (P < .001 for both) decreased FHR variability and variable decelerations with remifentanil. Labor: No difference in oxytocin use, route of birth, or length of active and second stage labor. Newborn: No difference in Apgar scores and cord blood pH. Neurologic and adaptive capacity scoring and naloxone administration not addressed. Feeding difficulties were similar between groups.
Thurlow et al60Randomized controlled trial 36 parturients, labor stage not reportedExperimental: PCA remifentanil 20 mcg bolus over 20 s, 3 min lockout interval, no background infusion Total doses not reported Control: IM meperidine 100 mg, plus promethazine (Phenergan) 25 mg or prochlorperazine (Compazine) 12.5 mg as antiemetic Nitrous oxide option available to both groups.Maternal: VAS pain scores 60 min and maximum pain scores during first 2 h after analgesia significantly lower (P= .0004 and 0.009, respectively) in the remifentanil group. Overall effectiveness of analgesia within 2 h of birth, rated by mothers and midwives, was higher (P= .002) in remifentanil group. No significant difference between groups in nausea and vomiting. No significant difference in minimum saturation between groups, but authors concluded that the overall saturation may have been lower for women receiving remifentanil. Fetal: No outcomes evaluated. Labor: Remifentanil associated with more (P= .04) nonvaginal routes of births; 6 of 7 women had also received epidural. Newborn: No difference in Apgar scores between groups.
Douma et al42Double-blind, randomized controlled trial 159 parturients in active phase laborExperimental: PCA remifentanil 40 mcg loading dose, 40 mcg/bolus, 2 min lockout interval, maximum dose limit 1200 mcg/h Control: PCA meperidine 49.5 mg loading dose, 5 mg bolus, 10 min lockout interval, total dose limit 200 mg, or PCA fentanyl (Sublimaze) 50 mcg loading dose, 20 mcg bolus, 5 min lockout interval, maximum dose limit 240 mcg/hMaternal: VAS pain scores decreased in all groups. Greatest decrease in pain scores with remifentanil at 1 h after administration (remifentanil vs meperidine, P < .05; remifentanil vs fentanyl, P < .01; meperidine vs fentanyl, P= NS). At 2 h after initiation of treatment, pain scores with meperidine were no different from baseline, and at 3 h, pain scores were not significantly different from baseline in all groups. Sedation increased in all groups; at 1 h and 2 h sedation was greater with remifentanil compared with meperidine and fentanyl (remifentanil vs meperidine, P < .05; remifentanil vs fentanyl P < .01). At 3 h, sedation scores with remifentanil were greater (P < .05) than with fentanyl only. Itching more common with remifentanil (P < .05). More crossover to epidural in meperidine group (P < .05). No difference in rates of nausea and vomiting. Overall satisfaction after birth greater in remifentanil group when compared with meperidine (P < .05). No difference in satisfaction between remifentanil and fentanyl or meperidine and fentanyl. Remifentanil and fentanyl associated with 1 or more periods of desaturation < 95% compared with meperidine (remifentanil vs meperidine, P < .0001; remifentanil vs fentanyl, P= NS; meperidine vs fentanyl, P < .05). Fetal: No difference in reactive/nonreactive FHR patterns. Labor: No difference in duration of labor, oxytocin use. Fentanyl associated with more spontaneous deliveries (P < .05). Newborn: No difference in Apgar scores, neurologic and adaptive capacity scores at 15 and 120 min, cord blood pH and base excess.