Lipophilic Opioids Research Articles

Caesarean Delivery: A Narrative Review on the Choice of Neuraxially Administered Opioid and Its Implications for the Multimodal Peripartum Pain Concept.

Nowadays, obstetrical anesthesia-related mortality is a very rare complication in industrialized countries. The recommended choice of intrathecal opioid for spinal anesthesia in the context of a multimodal peripartum pain management concept is discussed in this narrative review. Nowadays, there is a consensus that a perioperative multimodal pain concept should be used for caesarean delivery. This pain concept should include neuraxial opioids for spinal anesthesia, acetaminophen, NSAIDs, intravenous dexamethasone, and postoperative local or regional anesthetic procedures. Long-acting lipophobic opioids (diamorphine and morphine) have a significant analgesic advantage over short-acting lipophilic opioids (sufentanil and fentanyl). The risk of clinically relevant respiratory depression after neuraxial long-acting opioids is nowadays considered negligible, even if the data situation is weak in this regard. The question remains as to whether a pain concept that is ideally adapted to a neuraxial short-acting opioid shows benefit to a pain concept that is optimally adapted to neuraxial morphine. If long-acting opioids are used, the timing of each additional component of the multimodal analgesia strategy could ideally be adjusted to this longer duration of action.

Remimazolam: Is the quest for the holy grail of sedation during diagnostic or endoscopic interventions over?

Remimazolam: Is the quest for the holy grail of sedation during diagnostic or endoscopic interventions over?

A Comparison Between Dexmedetomidine and Clonidine as Adjuvants to Levobupivacaine in Labour Analgesia.

BackgroundThe epidural analgesia technique is effective for labor analgesia and combinations of various local anesthetics with lipophilic opioids like fentanyl are used. However, fentanyl can cause an increased incidence of pruritus, urinary retention, nausea, vomiting, giddiness, shivering, and respiratory depression. Dexmedetomidine and clonidine are selective alpha 2 agonists with analgesic properties and have been used via the neuraxial route with local anesthetics for the same without the side effects of fentanyl. Thus, the primary objective was to assess and compare the analgesic efficacy of the two-drug combinations by the visual analog scale (VAS) score.MethodsFifty-four primigravida women were randomly allocated in two groups of 27 each and were given an initial bolus of 10 mL of 0.125% levobupivacaine with dexmedetomidine 0.5 ug/kg in Group A and with clonidine 1 μg/kg in Group B. Subsequently, each patient received a background infusion rate of 10 mL/h, a bolus dose of 5 ml, and a lock-out interval of 10 min via a patient-controlled-analgesia (PCA) pump. The blood pressure, heart rate, and severity of pain using VAS were assessed. Durations of the stages of labor, rate of instrumental delivery, and cesarean section, side effects, maternal sedation, and neonatal Apgar scores were also recorded.ResultsVAS scores in both the groups progressively decreased to <3 by 15 min with significant differences at five, 10, 15, and 120 min being lower in group A. Onset of analgesia and time for maximum analgesia was significantly shorter in group A. There was a significant decrease in hemodynamic parameters from baseline in both groups. The fall in heart rate was significantly greater in Group A and at almost all the time intervals after baseline, diastolic blood pressure (DBP) was also lower in group A. Maternal motor blockade scores, the intensity of maternal sedation, the incidence of maternal complications, the duration of the first and second stage of labor, the rate of instrumental delivery and cesarean section, total analgesic dose and PCA bolus requirement, and neonatal Apgar scores did not show a significant difference between the two groups.ConclusionBoth dexmedetomidine and clonidine provide hemodynamically stable labor with a fall in heart rate and maternal blood pressure in the initial hours. Dexmedetomidine has the advantage of faster onset of analgesia and time for maximum analgesia.

Maternal haemodynamics during labour epidural analgesia with and without adrenaline.

Labour is one of the most painful experiences in a woman's life. Epidural analgesia using low-concentration local anaesthetics and lipophilic opioids is the gold standard for pain relief during labour. Pregnancy in general, particularly labour, is associated with changes in maternal haemodynamic variables, such as cardiac output and heart rate, which increase and peak during uterine contractions. Adrenaline is added to labour epidural solutions to enhance efficacy by stimulating the α2-adrenoreceptor. The minimal effective concentration of adrenaline was found to be 2μgmL-1 for postoperative analgesia. The addition of adrenaline may also produce vasoconstriction, limiting the absorption of fentanyl into the systemic circulation, thereby reducing foetal exposure. However, adrenaline may influence the haemodynamic fluctuations, possibly adding to the strain on the circulatory system. The aim of this study was to compare the haemodynamic changes after application of labour epidural analgesia with or without adrenaline 2μgmL-1. This was a secondary analysis of a single-centre, randomised double-blind trial. Forty-one nulliparous women in labour requesting epidural analgesia were randomised to receive epidural solution of bupivacaine 1mgmL-1, fentanyl 2μgmL-1 with or without adrenaline 2μgmL-1. The participants were monitored using a Nexfin CC continuous non-invasive blood pressure and cardiac output monitor. The primary outcomes were changes in peak systolic blood pressure and cardiac output during uterine contraction within 30min after epidural activation. The effect of adrenaline was tested statistically using a linear mixed-effects model of the outcome variables' dependency on time, adrenaline, and their interaction. After excluding three patients due to poor data quality and two due to a malfunctioning epidural catheter, 36 patients (18 in each group) were analysed. The addition of adrenaline to the solution had no significant effect on the temporal changes in peak systolic blood pressure (p=0.26), peak cardiac output (0.84), or heart rate (p=0.91). Furthermore, no significant temporal changes in maternal haemodynamics (peak systolic blood pressure, p=0.54, peak cardiac output, p=0.59, or heart rate p=0.55) were associated with epidural analgesia during 30min after epidural activation in both groups despite good analgesia. The addition of 2μgmL-1 adrenaline to the epidural solution is not likely to change maternal haemodynamics during labour.

Intrathecal catheter use after accidental dural puncture in obstetric patients: literature review and clinical management recommendations.

If an accidental dural puncture occurs, one option is to insert a catheter and use it as an intrathecal catheter. This avoids the need for a further injection and can rapidly provide labour analgesia and anaesthesia for caesarean section. However, there are no recommendations for managing intrathecal catheters and, therefore, significant variation in clinical practice exists. Mismanagement of the intrathecal catheter can lead to increased motor block, high spinal anaesthesia, drug error, hypotension and fetal bradycardia. Care must be taken with an intrathecal catheter to adhere to strict aseptic technique, meticulous labelling, cautious administration of medications and good communication with the patient and other staff. Every institution considering the use of intrathecal catheters should establish a protocol. For labour analgesia, we recommend the use of dilute local anaesthetic agents and opioids. For caesarean section anaesthesia, gradual titration to the level of the fourth thoracic dermatome, with full monitoring, in a facility equipped to manage complications, should be performed using local anaesthetics combined with lipophilic opioids and morphine or diamorphine. Although evidence of the presence and duration of intrathecal catheters on the development of post-dural puncture headache and need for epidural blood patch is limited, we suggest considering leaving the intrathecal catheter in for 24 hours to reduce the chance of developing a post-dural puncture headache while maintaining precautions to avoid drug error and cerebrospinal fluid leakage. Injection of sterile normal saline into the intrathecal catheter may reduce post-dural puncture headache. The level of evidence for these recommendations was low.

Comparison of dexmedetomidine and lipophilic opioids as adjuvants to local anesthetics for epidural labor analgesia: a meta-analysis of randomized controlled trials

The aim of this study is to evaluate the benefits of dexmedetomidine in epidural labor analgesia compared with lipophilic opioids. The databases of PubMed, Embase, Cochrane Library, Web of Science, Wanfang, and SinoMed were searched from inception to Mar. 25, 2021 for randomized controlled trials (RCT) that assessed dexmedetomidine versus lipophilic opioids as adjuvants to local anesthetics in epidural labor analgesia. Meta-analyses were conducted with RevMan 5.3, and a random-effects model was adopted. A total of 11 RCTs involving 1099 parturients were enrolled. The results showed that, compared with the control group, dexmedetomidine significantly reduced Visual Analogue Scale (VAS) scores both at 30 minutes after induction [weighted mean difference (WMD) = –0.40, 95% CI: –0.61 to –0.20] and on delivery (WMD = –0.83, 95% CI: –1.15 to –0.50), reduced analgesic consumption (WMD = –6.29 mL, 95% CI: –10.49 to –2.10), shortened the duration of the first (WMD = –9.58 minutes, 95% CI: –18.12 to –1.04) and second (WMD = –1.66 minutes, 95%CI: –3.20 to –0.12) stage of labor, increased maternal bradycardia [risk ratio (RR) = 2.44, 95% CI: 1.31 to 4.53] and motor blockade (RR = 5.30, 95% CI: 2.21 to 12.73), reduced nausea/vomiting (RR = 0.34, 95% CI: 0.20 to 0.57), pruritis (RR= 0.19, 95%CI: 0.06 to 0.58) and shivering (RR = 0.37, 95% CI: 0.18 to 0.77). There was no significant difference between groups in the rate of instrumental delivery (p = 0.68), and cesarean delivery (p = 0.40), Apgar scores at 1 minute (p = 0.24), at 5 minutes (p = 0.36), and the umbilical arterial PH (p = 0.16). In summary, compared to lipophilic opioids, dexmedetomidine for epidural labor analgesia reduced analgesic agent consumption and resulted in fewer maternal complications.

Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta- analysis of randomized controlled trials

BackgroundShivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering.ObjectiveWe performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD.MethodsThis review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc.ResultsTwenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10–0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18–32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09–0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14–5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result.ConclusionIT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.

Oral morphine drops for prompt relief of breathlessness in patients with advanced cancer-a randomized, double blinded, crossover trial of morphine sulfate oral drops vs. morphine hydrochloride drops with ethanol (red morphine drops).

Episodic breathlessness is frequent in palliative cancer patients. Opioids are the only pharmacological agents with sufficient evidence in treatment. In Denmark, the main recommendation is red morphine drops (RMD), an off-label solution of morphine, ethanol, and red color (cochenille) described since 1893 (Pharmacopoea Danica). In 2015, the Danish Medicines Agency increased focus on off-label medicines and recommended registered morphine drops without ethanol instead. However, our palliative patients told us that RMD was better. For that reason, we conducted a clinical trial to clarify any perceived difference between the two types of drops. We conducted a randomized, double blinded, crossover trial. Patients were asked to perform standardized activity (2-min walk) aiming to provoke breathlessness. Primary endpoint (breathlessness NRS) and secondary endpoints (saturation, pulse, respiratory frequency) were measured before (t = 0) and after test medicine at t = 1, t = 3, t = 5, t = 10, and t = 20 min. After 2-4 days (washout period), the patients repeated the test, receiving the alternative drops in a blinded setup (crossover). In the first 3 min, the relative drop in breathlessness for morphine drops with ethanol (RMD) was significant more than for morphine drops without ethanol. We found no significant difference in secondary endpoints. A conclusion could be that ethanol might facilitate morphine absorption in the mouth. Our results needs further research of opioid absorption in the mouth as well as trials, testing morphine vs. more lipophilic opioids. The RMD drops are cheap, easy to use, and noninvasive and keep the patient independent of health care professionals.

Effects of Adrenaline on maternal and fetal fentanyl absorption in epidural analgesia: A randomized trial.

BackgroundThe combination of low‐dose local anesthesia and lipophilic opioids such as fentanyl is established as a standard solution for labor epidural analgesia. Fentanyl increases efficacy, but may have negative effects on the neonate in terms of reduced neonatal neurologic and adaptive capacity scores and breast feeding. We hypothesized that addition of adrenaline 2 μg/mL to a solution of bupivacaine 1 mg/mL and fentanyl 2 μg/mL would reduce the systemic uptake of fentanyl, resulting in reduced serum fentanyl in the fetus at birth.MethodsForty‐one nulliparous women requesting epidural analgesia were randomized to epidural analgesia with or without adrenaline. Blood samples were drawn from the mother with regular intervals, and at delivery. An umbilical vein blood sample (used as a proxy for fetal exposure) was drawn after clamping.ResultsThere were no significant differences between the groups in fentanyl concentrations in the umbilical vein and maternal serum at birth. There was a significantly lower mean area under the maternal serum‐concentration curve for the first 2 hours of treatment in the adrenaline group (mean difference 0.161 nmol h/L [0.034; 0.289], P = .015), implying slower systemic uptake in the adrenaline group initially. There were no significant differences in treatment duration, motor block, Apgar scores, umbilical pH and base excess, or mode of delivery.ConclusionsThe addition of adrenaline to an epidural solution containing fentanyl lowered maternal systemic serum fentanyl concentration during the first 2 hours, but did not lower serum fentanyl concentration in the umbilical vein and mother at delivery.

A double-blind randomized control trial to compare the effect of varying doses of intrathecal fentanyl on clinical efficacy and side effects in parturients undergoing cesarean section

Background and Aims:It is a common practice to add intrathecal lipophilic opioids to local anesthetics to improve the quality of subarachnoid block. This study was designed to find a dose of intrathecal fentanyl, which can improve the quality of surgical anesthesia with minimal side effects in parturients undergoing cesarean section under spinal anesthesia with intrathecal bupivacaine.Material and Methods:In a prospective randomized double-blind study, 243 parturients undergoing cesarean section under spinal anesthesia were randomly allocated to receive 10, 15, or 25 μg of intrathecal fentanyl with 10 mg of 0.5% hyperbaric bupivacaine. Patients were assessed for clinical efficacy by measuring pain score, need for rescue analgesia, conversion to general anesthesia, and complaints of inadequacy of surgical anesthesia by the surgeon. The side effects assessed were pruritus, nausea, vomiting, dizziness, and decrease in saturation and respiratory rate. In addition, neonatal APGAR score, patients' hemodynamics, need for vasopressors, onset and duration of sensory, and motor block were measured.Results:Patients receiving 25 μg of fentanyl had a significantly higher incidence of pruritus, nausea, and dizziness in addition to a significantly prolonged sensory and motor block (P < 0.001). All patients in three groups had adequate surgical anesthesia with no statistically significant difference in the onset of block, quality of surgical anesthesia, pain scores, neonatal APGAR score, hemodynamic variables, and need for vasopressor.Conclusion:For patients undergoing cesarean section, 10 or 15 μg of intrathecal fentanyl with 10 mg of bupivacaine provided adequate surgical anesthesia and analgesia with minimal side effects.

Spinal Fentanyl Versus Sufentanil for Postoperative Analgesia After C-section: A Double-blinded Randomized Trial

(Acta Anaesthesiol Scand 2016) [Epub ahead of print] Several studies have shown that the addition of opioids, such as morphine, to an intrathecal (IT) local anesthetic solution prolongs the effective postoperative analgesia in women undergoing cesarean section. Two of the most commonly administered lipophilic opioids are fentanyl and sufentanil. As there are few studies that compare these 2 agents, the authors of the present study investigated the effective analgesia duration, postoperative morphine requirement, and incidence of side effects for both IT fentanyl and sufentanil.

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials.

ObjectiveThe addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted.MethodsA comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I2 tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg’s funnel plots and Egger’s linear regression test were used to detect any publication bias.ResultsThis study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = −1.0 min, 95% CI −1.5 to −0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001).ConclusionBupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.

Side Effects and Efficacy of Neuraxial Opioids in Pregnant Patients at Delivery: A Comprehensive Review.

Neuraxial opioids are an integral part of obstetric anaesthesia and have contributed to greatly improved analgesia for labour and caesarean delivery, both intraoperatively and postoperatively. Despite these advantages, neuraxial opioids may be associated with a number of side effects, some of which (such as respiratory depression), although rare, may be associated with significant morbidity and mortality. The risk of respiratory depression appears to be increased with less lipophilic opioids such as morphine but can be reduced with careful patient selection and monitoring. Other side effects such as pruritus and nausea and vomiting appear to be dose-related and so can be limited by choosing the appropriate dose to optimise analgesia whilst limiting the adverse effects. Urinary retention, the potential neurotoxic effects of neuraxial opioids and the postulated effects on the foetus are also considered but currently it is felt there is not enough evidence to make strong recommendations with regard to specific drugs or dosage. This review aims to discuss the mechanism and incidence of these side effects as well as, where possible, their prevention.

Transient loss of voice during labour analgesia.

Sir, A 30-year-old full term American Society of Anesthesiologists 1 primigravida patient was administered labour analgesia (LA) on demand at 4-5 cm cervical dilation employing combined spinal epidural (CSE) technique. In sitting position, assuring asepsis, 18 g epidural catheter was sited in L2-3 space threaded up to 10 cm, checked and fixed. After that, 1cc of 0.125% preservative free isobaric bupivacaine (1cc of 0.25% preservative free bupivacaine double diluted with sterile normal saline) and 10 μg fentanyl was injected intrathecally via 26 g Quincke needle at L3-4 space. Maternal and foetal vital parameters remained stable. She had satisfactory pain relief in 10 min and was chatting comfortably when suddenly after 12 min, we noticed loss of voice (she was unable to talk). Other than that there was no neurodeficit or dyspnoea. Spinal level was limited to T6. She was fully awake, oriented and continued communication with us by writing. All maternal and foetal vital parameters remained normal. She was pain free and her labour progressed normally. She was worried but not hysterical. No further abnormality was revealed in neurology consultation. As no further deterioration was noted, we counselled the patient and relatives regarding this event being a rare but reversible drug side effect and reassured them about both maternal and foetal well-being. Epidural bolus was held off, which otherwise would be given at 30 min after spinal injection. By 45 min of the event the phonation started returning and by 1 h she was able to speak normally. Simultaneously cervix was found to be fully dilated and she went on to have a normal vaginal delivery. Ten millilitre 0.25% bupivacaine was given epidurally for episiotomy suturing. The epidural catheter was removed after suturing. The post-operative recovery, hospital stay and follow up for 3 months was uneventful. Cerebral complications of preeclampsia, thrombo-embolic phenomena, absence seizure or high spinal can mimic symptoms of transient ischaemic attack in a parturient. However, our patient did not fit into any of these categories. Kuczkowski and Goldsworthy[1] reported a case of a previously healthy parturient who received 10 μg of fentanyl combined with 2.5 mg of bupivacaine intrathecally as a part of CSE technique for LA and At 4 min after intrathecal injection she suddenly developed transient aphonia and aphagia. The pinprick sensory level of analgesia was found to be at T3 and her symptoms resolved in 20 min. Gupta et al.[2] reported aphonia and aphagia in a male patient posted for lower limb debridement at 3 min after receiving 12.5 mg heavy bupivacaine with 25 μg fentanyl intrathecally which recovered spontaneously in 10-15 min. In both cases the authors believe extensive cephalad spread of fentanyl through the Cerebrospinal fluid (CSF) as the cause for neurological symptoms. There has been a study which noted rapid cephalad spread of fentanyl in the cervical CSF after lumbar administration.[3] Sudden onset, life-threatening respiratory depression have been reported following administration of intrathecal fentanyl for labour analgesia which suggest that lipophilic opioids may move rapidly from lumbar cistern to brainstem level via CSF.[4] There may be more rapid rise in CSF concentrations of drug due to pregnancy related changes. Rapid clearance of fentanyl from the CSF might explain the transient nature of symptoms. Some cases have been reported where similar side effects were noted to be reversed using opioid antagonists naloxone and nalbuphine[5] supporting the cause to be the opioid. Many similar unreported incidences may have been attributed to over anxious and hysterical nature of patients. CSE using fentanyl is one of the established techniques for labour analgesia with minimal side effects. It is necessary to be aware of this rare side effect and maintain composure, provide reassurance to patient and reverse drug effect if needed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Transient aphonia following spinal anesthesia in a parturient: A case report

Spinal anesthesia is the preferred technique of administering anesthesia for elective cesarean section (CS). Hypotension, failed spinal anesthesia, postdural-puncture headache, cauda equina syndrome are a few complications that may occur but neurological complications particularly aphonia are quite rare. The use of lipophilic opioids as adjuvants with local anesthetics are considered as culprit but the exact mechanism remains unidentified. We report such presentation in our patient and discuss the likely cause.

Association of lipophilic opioids and hyperbaric bupivacaine in spinal anesthesia for elective cesarean section. Randomized controlled study.

To evaluate the efficacy and side-effects of fentanyl and sufentanil combined with hyperbaric spinal bupivacaine in elective cesarean section. A prospective, randomized, double-blind study with 64 term parturients, distributed into 2 groups according to the opioid combined with hyperbaric bupivacaine 0.5% (10mg): GF - fentanyl (25 µg) and GS - sufentanil (5.0 µg). The latency and maximum sensory block level; degree and duration of motor block; duration and quality of analgesia; maternal-fetal repercussions were evaluated. This was an intention-to-treat analysis with a 5% significance level. The latency period, maximum sensory block level, motor block degree and perioperative analgesia were similar in both groups. Motor block and analgesia had a longer duration in the sufentanil group. Maternal adverse effects and neonatal repercussions were similar. The incidence of hypotension was higher in the fentanyl group. In both groups, there was a predominance of patients who were awake and either calm or sleepy. The addition of fentanyl and sufentanil to hyperbaric subarachnoid bupivacaine was shown to be effective for the performance of cesarean section, and safe for the mother and fetus. Analgesia was more prolonged with sufentanil.

English

BACKGROUND: Addition of lipophilic opioids like Fentanyl and Sufentanil to local anaesthetic for spinal anaesthesia has shown to prolong the duration of analgesia. This study was carried out to study (a) Comparison of effect of Fentanyl and Sufentanil added to Bupivacaine on onset and duration of anaesthesia in Cesarean Section. (b) To compare the quality and duration of analgesia between the two opioids and (c) To compare the effect on neonatal outcome. METHODS: 50 parturients of ASA grade 1 and 2 undergoing Cesarean Section were randomized into two groups of 25 each. Group F received 2.5 ml 0.5% Bupivacaine heavy + inj. Fentanyl 0.25 ml (12.5 mcg) and Group S received 2.5 ml 0.5% Bupivacaine heavy + inj. Sufentanil 0.1 ml (5 mcg) intrathecally. Onset of sensory and motor blockade was noted in all the patients. Haemodynamic parameters were recorded every 5 minutes for first 30 minutes and then every 15 minutes till the completion of surgery. Duration of sensory and motor sensory blockade was observed post operatively. RESULT: Both the groups were stable haemodynamically. Both the groups were comparable regarding the duration of sensory and motor block, but the total duration of effective analgesia was significantly longer in Sufentanil group. Pruritus was significant side effect in Sufentanil group. Neither the mother nor the neonate had respiratory depression. CONCLUSION: Addition of Sufentanyl to intrathecal bupivacaine provides longer duration of analgesia as compared to intrathecal fentanyl-bupivacaine.

Synergistic Interaction between Fentanyl and Bupivacaine Given Intrathecally for Labor Analgesia

Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans. Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity. The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction. The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.

A comparison of intrathecal dexmedetomidine verses intrathecal fentanyl with epidural bupivacaine for combined spinal epidural labor analgesia

Context: Combined spinal epidural (CSE) analgesia technique is effective for labor analgesia and various concentrations of bupivacaine and lipophilic opioids like fentanyl have been studied. Dexmedetomidine is a highly selective alpha 2 adrenoreceptor agonist with analgesic properties and has been used intrathecally with bupivacaine for prolonged postoperative analgesia. Recent reviews have shown that it is highly lipophilic and does not cross placenta significantly.Aim: The aim of this study is to compare the duration and quality of analgesia, maternal and neonatal outcomes after CSE labor analgesia with intrathecal dexmedetomidine and intrathecal fentanyl followed by epidural bupivacaine.Settings and Design: A randomized observational study with 112 parturients in a tertiary care hospital.Materials and Methods: 112 parturients were randomly divided to two groups. Group D (n = 58) received dexmedetomidine 10 μg and group F (n = 54) received fentanyl 20 μg intrathecally for labor analgesia. The time of onset, time to maximum analgesia, duration and quality of analgesia were noted. Maternal parameters of heart rate, noninvasive blood pressure, motor block and side-effects of pruritus, nausea and vomiting were recorded. Neonatal outcome in terms of mode of delivery, neonatal APGAR score, time to first cry, need for resuscitation, umbilical cord blood pH, initiation of breast feeding, Neurologic and Adaptive Capacity Score at 24 h and exclusivity of breast feeding at 6 weeks were recorded.Results: Duration of analgesia was 160.54 ± 52.4 min with dexmedetomidine and 124.1 ± 46.93 min with fentanyl (P < 0.001). Visual analog score (VAS) recorded at maximal analgesia was significantly lesser in the fentanyl group compared to dexmedetomidine group, denoting a significantly deeper level of analgesia with fentanyl. However, all the mothers in the dexmedetomidine group achieved a VAS <3 and were satisfied with the quality of analgesia. About 74% patients in the fentanyl group experienced pruritus after intrathecal injection whereas none of the mothers in dexmedetomidine group experienced pruritus (P < 0.001). There were no significant differences in neonatal outcome between the two groups.Conclusion: 10 μg dexmedetomidine intrathecally provides a longer duration of analgesia with lesser incidence of pruritus compared to 20 μg fentanyl intrathecally for CSE labor analgesia with comparable neonatal side-effects.

The median local analgesic dose of intrathecal bupivacaine with hydromorphone for labour: a double-blind randomized controlled trial

Neuraxial hydromorphone has been reported to provide rapid onset of labour analgesia, effective segmental pain relief, and a longer duration of action than commonly used lipophilic opioids. This study was conducted to test the hypothesis that intrathecal hydromorphone reduces the dose requirement for intrathecal bupivacaine to induce rapid analgesia for women in the first stage of labour. In this double-blind randomized controlled sequential allocation trial, 88 labouring parturients received combined spinal-epidural analgesia at 2-6 cm cervical dilation. Participants received intrathecal bupivacaine alone or bupivacaine plus hydromorphone 100 μg with the bupivacaine dose determined using up-down sequential allocation. An effective dose was defined as a visual analogue pain score of ≤10 mm (on a 100-mm pain scale) reported within 20 min of injection. The median effective doses were calculated using the formula of Dixon and Massey and verified using isotonic regression. A decrease was observed in the median local analgesic doses (effective dose [ED50]) estimated according to the formulas of Dixon and Massey, with a between-group difference of -0.45 mg. The precision of the estimate was wide-ranging (95% confidence interval -1.23 to 0.33), so no definitive conclusion can be drawn. Further research is needed to determine whether or not intrathecal hydromorphone 100 μg changes the dose of intrathecal bupivacaine required to induce labour analgesia within 20 min. The trial was conducted in 2007 prior to widespread acceptance of the standard for clinical trial registration.