Why Intrathecal Fentanyl Is Preferred to Other Opioids - Essay Example

Why Intrathecal Fentanyl Is Preferred To Other Opioids: A Review of Literature Fentanyl is a synthetic opioid related to the phenylpiperidines. The actions of fentanyl and its congeners, sufentanil, remifentanil, and alfentanil, are similar to those of other -receptor agonists. Alfentanil is seldom used now. Fentanyl is a popular drug in anesthetic practice because of its relatively shorter time to peak analgesic effect, rapid termination of effect after small bolus doses, and relative cardiovascular stability. Fentanyl is approximately 100 times more potent than morphine, and sufentanil is approximately 1000 times more potent than morphine. These drugs are most commonly administered intravenously, although both also are commonly administered epidurally and intrathecally for acute postoperative and chronic pain management. Fentanyl and sufentanil are far more lipid soluble than morphine; thus the risk of delayed respiratory depression from rostral spread of intraspinally administered narcotic to respiratory centers is greatly reduced (Tucker, AP., Mezzatesta, J., Nadeson, R., and Goodchild, CS., 2004). Remifentanil was developed in an effort to create an analgesic with a more rapid onset and predictable termination of effect. The potency of remifentanil is approximately equal to that of fentanyl. The pharmacological properties of remifentanil are similar to those of fentanyl and sufentanil (Ross AK, Davis PJ, Dear GL, et al., 2001). They have similar incidences of nausea, vomiting, and dose-dependent muscle rigidity. Nausea, vomiting, itching, and headaches have been reported when remifentanil has been used for conscious analgesia for painful procedures (Egan TD., 2000). Intracranial pressure changes are minimal when ventilation is controlled. Seizures after remifentanil administration have been reported. Remifentanil has a more rapid onset of analgesic action than fentanyl or sufentanil (Saravanakumar K, Garstang JS, Hasan K., 2007). Analgesic effects occur within 1 to 1.5 minutes. Remifentanil is unique in that it is metabolized by plasma esterases. Elimination is independent of hepatic metabolism or renal excretion, and the elimination half-life is 8 to 20 minutes (Owen MD, Poss MJ, Dean LS, et al., 2002). There is no prolongation of effect with repeated dosing or prolonged infusion (Olufolabi AJ, Booth JV, Wakeling HG, et al., 2000). Age and weight can affect clearance of remifentanil, requiring that dosage be reduced in the elderly and based on lean body mass. Remifentanil hydrochloride is useful for short, painful procedures that require intense analgesia and blunting of stress responses (Volmanen P, Akural EI, Raudaskoski T, et al., 2002). The titratability of remifentanil and its consistent, rapid offset make it ideally suited for short surgical procedures where rapid recovery is desirable. Remifentanil also has been used successfully for longer neurosurgical procedures, where rapid emergence from anesthesia is important (Blair JM, Hill DA, Fee JP., 2001). However, in cases where postprocedural analgesia is required, remifentanil alone is a poor choice (Babenco HD, Conard PF, Gross JB., 2000). Fournier and co-workers in their study published in Anesthesia Analgesia compare the postoperative analgesic effects of intrathecal fentanyl and sufentanyl with the set end points being the parameters of onset, quality, and duration of action. The authors undertake a detailed literature review, where the reader understands the perspectives and aim of this study in a clear manner. Intrathecal opioid analgesia with lipophilic opioids is a well accepted anesthetic procedure for postoperative and labour pain (Cowan, CM, Kendall, JB., Barclay, PM., and Wilkes, RG., 2002). Drugs like sufentanil and fentanyl are widely used for pain relief during labor, and they have predictable onset and end points of action. However, these drugs are not often used for postoperative analgesia (Meininger, D. et al., 2003). This study has investigated the use of continuous spinal anesthesia as the mode of investigation for lower limb orthopedic procedures in the elderly patients. The authors had retained the intrathecal catheter in the postoperative phase for administration of intrathecal drugs. Since overnight observations of these elderly patients were not possible, short acting lipophilic opioids such as sufentanil or fentanyl were logical considerations. The main reason in favour such drugs was the advantage of no need for prolonged monitoring and safety of the patients since the risk of respiratory is predominantly limited to first 2 hours of intrathecal injection (Siddik-Sayyid, SM., Aouad, MT., Jalbout, MI., Zalaket, MI., Berzina, CE., and Baraka, AS., 2002). The authors also recorded studies of the efficacy of such drugs following lower extremity revascularization surgery with the optimum dose being 40 g of intrathecal fentanyl. This amount of dosage provides satisfactory analgesia with rapid onset of action, and duration of action around 5 h. The intrathecal sufentanil is more commonly used in labor anaesthesia, and its postoperative analgesic properties are not well documented in literature (Fournier, R., Van Gessel, E., Weber, A., and Gamulin, Z., 2000). Therefore, the authors compared the analgesic characteristics of fentanyl and sufentanil in terms of onset, quality, and duration of analgesia in postsurgical pain relief after total hip arthroplasty in elderly patient population. The intrathecal dose of fentanyl was mentioned earlier, and sufentanil was used in the dose of 7.5 g. To analyze the efficacy and safety parameters, the ancillary end points were 24-h additional analgesic requirements, the hemodynamic changes, and the adverse effects. There were slightly shorter onset and longer duration of action observed in sufentanil, but the differences were not statistically significant. These two comparison groups did not demonstrate much of difference in terms of analgesic requirements for duration of 24 h. The authors observed that the hemodynamic variations during the first hour after intrathecal injection were similar in both groups, and the patients in both the groups did not suffer much of decrease in the mean arterial pressure, although the range was a little more in the sufentanil group. The heart rates remained stable, and none of the patients required augmentation by inotropic agents, such as, ephedrine and atropine. Within the first hour as expected almost equal number of patients in both the groups demonstrated oxygen saturation tending towards a lower range, and with oxygen adjustment, this resolved, and none of the patients did demonstrate any overt signs of respiratory failure. Sedation score never exceeded 2 in any of these patients, and side effects were in the range of mild pruritus and nausea and vomiting, but the incidence was not alarming (Fournier, R., Van Gessel, E., Weber, A., and Gamulin, Z., 2000). Although this study had no controls for ethical reasons, the findings when compared to similar findings from other literature are very thought provoking and interesting in the sense that these might point to the standards and guidelines for evidence-based anesthesiology practice. In literature, there are only a limited number of reports documenting the use of single bolus injection of intrathecal fentanyl alone for postoperative analgesia, especially in hip surgery. Other literatures have compared dosages of 5 to 50 g for relief of pain following lower extremity revascularization surgery. From these studies, an optimal dose of 40 g was demonstrated to be providing an excellent quality of analgesia within 10 minutes that lasted for 5 hours. The quality of analgesia was excellent in these authors' study with complete pain relief in most of the patients. The authors ascribed their finding of comparatively lower duration of action to the type of surgery, which is very valid. From literature, when it is used in a single dose of 25 g for early postoperative phantom limb pain and post-amputation stump pain, comparably, the onset and duration of action were similar except in the later cases, the duration was much longer in the range of 8 h. Continuous infusion for a period of 24 h at a reduced dose would not produce an acceptable and satisfactory postoperative analgesia in hip surgery from other authors. Literature also indicate marked differences in obstetrical and postoperative pain patterns, since in a series of labour patients, the doses of 35-45 g of intrathecal fentanyl would produce excellent analgesia within 10 minutes of injection, but with the disadvantage of a far shorter duration of 90 minutes (Fournier, R., Van Gessel, E., Weber, A., and Gamulin, Z., 2000). Literature provides mention of intrathecal sufentanil as a postoperative analgesic in a case report of bilateral total knee replacement. The dose of 5 g of sufentanil produced excellent and prolonged analgesia, but this required respiratory assistance and intravenous opioid antagonism due to precipitation of respiratory depression, raising questions about its safety. In the study by Fournier et al., 7.5 g of sufentanil resulted in a rapid onset of pain relief and complete alleviation of pain in all participants, and the duration was in the range of 4 h. Some researchers have compared post cesarean section analgesia in combination with intrathecal bupivacaine and provided sustainable complete pain relief (Manullang, TR, Viscomi, CM, and Pace, NL., 2000). Intrathecal sufentanil has been investigated widely as a sole intrathecal analgesic in obstetric analgesia. Different studies have indicated that 5 to 10 g of this agent given intrathecally was able to provide rapid pain relief within 5 to 10 minutes, although with a lower duration of action in the range of 60-95 minutes (Hughes, D., Hill, D., and Fee, JPH., 2001). Pharmacologically, sufentanil is twice as lipophilic than fentanyl. Studies have revealed that intrathecal sufentanil tends to demonstrate a quicker onset of action. Fentanyl has been acclaimed to be a largely lipophilic compound, it may act at a much faster rate to allow detection of the onset of action time with conventional testing methods. Pruritus is common adverse effect of this category of drugs, but due to unknown reasons patients in labour are more prone to this adverse effects, and the elderly individuals are less predisposed to this side effect. Comparison between fentanyl and sufentanil revealed that incidence of pruritus is less in elderly undergoing hip surgery in the fentanyl group than those who received sufentanil (Fournier, R., Van Gessel, E., Weber, A., and Gamulin, Z., 2000). In the descriptive discourse published in British Journal of Anaesthesiology, Rawal presents a discussion on suitable anaesthesia for day care surgery. Major advances in anaesthetic techniques that uses agents of short duration and regional techniques is enabling the providers to create protocols for patients with surgical procedures with minimal trauma to be discharged early avoiding admission. The number of day care surgeries is increasing across the world with top priorities on alertness, ambulation, analgesia, and alimentation. Of these, the pain management is perhaps the most important parameter. The author has discussed the roles of opioids in day care surgery, and despite objections against these agents due to postoperative nausea and vomiting, the author has cited reports stating that at equianalgesic dosage, the emetic effects of all opioids appear to be similar, and pain itself is a stimulus for nausea. Therefore, abolishing pain would itself act as an antiemetic. Average recovery time is not significantly prolonged by use of intraoperative opioids. The author quotes studies that indicate early ambulation and discharge after fentanyl and alfenatanil based anesthetic techniques (Rawal, N., 2001). The ultra-short-acting remifentanil has been observed to be associated with a predictable and rapid recovery independent of duration of infusion. It has the benefits of rapid postoperative recovery and virtual absence of respiratory depression, but the precluding disadvantage is that of immediate requirement of longer acting opioid or an alternative analgesic as soon as the effect of the drug wears off. Intraoperative remifentanil has been shown to be associated with acute opioid tolerance leading to increased postoperative pain and opioid consumption (Guignard, B., Menigaux, C., Dupont, X., Fletcher, D., and Chauvin, M., 2000). In their critical review, Rathmell et al. has explored the role and current use of intrathecal drugs in the treatment of acute pain. The authors briefly explain the current evidence of the pharmacology of these agents (Rathmell, JP, Lair, TR., and Nauman, B., (2005). Others have also studied the comparative pharmacodynamics of these agents such as fentanyl, sufentanil, and alfentanil and have found that their compartmentalization following intrathecal administration is a correlate of their lipid solubility. Intrathecal opioids penetrate the spinal cord and dura mater to end the epidural space. Within the spinal cord some of the drugs bind to the specific receptors and some eventually reach the circulation by venous uptake, and sum of this compartmentalization is responsible for the clinical effects that they demonstrate. They found that alfentanil has high clearance from spinal cord into plasma, fentanyl rapidly distributes into epidural space and fat, and sufentanil has high spinal cord volume of distribution (Ummenhofer, WC., Arends, RH., Shen, DD., and Bernards, CM., 2000). Any drug within the intrathecal space is rapidly distributed to brain, and even lipophilic agents like sufentanil can be detected within the cisterna magna within 30 min of administration (Swenson JD, Owen J, Lamoreaux W, et al., 2001). All these lipophilic opioids move and get rapidly distributed within the CSF, and this may account for their small but probable risk for respiratory depression (Eisenach JE., 2001). Fentanyl and sufentanil are the most commonly used lipophilic opioid drugs for intrathecal delivery. Both these drugs have rapid onset of analgesia and short duration of action, and for this reason they are used in labour and delivery (Connelly, NR. and Dunn, SM., 2000) and also as an additive in spinal anesthesia for ambulatory procedures for more rapid onset, better surgical block, and more rapid recovery of motor functions that allow earlier discharge (Pinder, AJ and Dresner, M, 2002). Meta-analysis of controlled trials demonstrated sufentanil and fentanyl both provide comparable analgesia in early labour, but with more frequent incidence of pruritus, with duration varying on the stage of labour (Bucklin BA, Chesnut DH, Hawkins JL., 2002). A dose of 10 g of sufentanil in combination with 2.5 mg of bupivacaine could provide a lasting analgesia if given in early labour provided catheters are used for intermittent delivery than a single-shot technique (Norris MC, Fogel ST, Conway-Long C., 2001). For cesarean delivery, however, fentanyl (Ben-David, B., Miller, G., Gavriel, R., and Gurevitch, A., 2000) and sufentanil (Fontaine, P., Adam, P., and Svendsen, KH., 2002) demonstrated equivalent actions in terms of faster onset of block, improved intra and postoperative analgesia that was durable with decreased nausea and vomiting (Sanli, S., Yegin, A., Kayacan, N., Yilmaz, M., Coskunfirat, N., and Karsli, B., 2005). Brief outpatient surgery is another rapidly developing area that is experiencing the use of intrathecal lipophilic opioids. The mode of use is addition of sufentanil or fentanyl to bupivacaine or lidocaine to deliver a block with rapidity, improved analgesia without motor impairment that would cover the intraoperative period and postoperative period (Lee, YY., Kee, WDN., Muchhal, K., and Chan, CK, 2005). Researchers have reported patients receiving 20 mg of 0.5% lidocaine in dextrose with 20 g of fentanyl for knee arthroscopy were ready for discharge within 45 min following anesthesia with postoperative analgesia ranging for up to 3 h. (Ben-David, B., Miller, G., Gavriel, R., and Gurevitch, A., 2000). Addition of fentanyl to small doses of hyperbaric bupivacaine enhances the quality of sensory block without the risk of prolonged motor blockade (Teoh, WHL and Sia, ATH, 2003). Connelly and coworkers have studied the comparison of epidural sufentanil and its effectiveness in providing a durable analgesia for 2 hours with a scope for early ambulation postoperatively (Connelly NR, Mainkar T, El-Mansouri M, et al., 2000). The authors reported in another study the utility of fentanyl for epidural administration in early labour. Fentanyl has the advantage of the ease of use, since the ampoule is the dose (Connelly, NR., Parker, RK., Vallurupalli, V., Bhopatkar, S., and Dunn, S., 2000). Despite its advantages, it was not known whether fentanyl would be the drug of choice for such purpose with respect to the duration of analgesia and adverse effects in nulliparous patients in the early stage of labour. The literature on labour analgesia favours intrathecal administration opioids with or without local anaesthetics (Rofaeel, A., Lilker, S., Fallah, S., Goldszmidt, E., and Carvalho, J., 2007). The potency ratio of sufentanil and fentanyl had been shown to be 1:5, and with the use of such concentration, researches have concluded that epidural fentanyl has several advantages over sufentanil in labour analgesia (Capogna, G., Camorcia, M., and Columb, MO., 2003). Moreover later research has revealed that labour pain relief using 7.5 g of intrathecal sufentanil results in a more frequent incidence of non reassuring fetal heart rate recording (Tacker SB, Stroup D, Chang M., 2002) and uterine hyperactivity, although it does not result in serious maternal or neonatal morbidity. This makes a valid point against the concept that onset of rapid analgesia is not the sole causative factor in intrathecal opioid associated uterine hyperactivity and fetal heart rate abnormalities (Van de Velde, M., Teunkens, A., Hanssens, M., Vandermeersch, E., and Verhaeghe, J., 2004). Walldn and coworkers have reported that remifentanil in small doses delays gastric emptying that is not influenced by body posture (Walldn, J., Thrn, S., and Wattwil, M., 2004). Therefore, this agent may be particularly prone to produce side effects perhaps through a central mechanism following crossing the blood brain barrier following intrathecal administration (Spiegel TA, Fried H, Hubert CD, et al., 2000). The findings from literature have been summarized in the clinical review paper by Minty et al. where they have examined the safety and efficacy of single-dose intrathecal opioids (Minty, R.G., Kelly, L., Minty, A., and Hammett, D.C., 2007). Intrathecal narcotics can serve as an effective means of labour analgesia (Leslie NG., 2000). Intrathecal narcotics can be useful tools in obstetric anaesthesia due to the fact that pain in labour, especially during the first stage of labour, and their effects are not neutralized by antagonists given by other routes (Canadian Institute for Health Information, 2004). Intrathecal surfentanil has a faster onset and longer duration of action but comparably similar to intrathecal bupivacaine, although there is a higher chance of fetal bradycardia without any increase in the rate of cesarean section (Mardirosoff C, Dumont L, Boulvain M, Tramer MR., 2002). On the face of the fact that epidural analgesia in labour has shown that epidural relieves pain better at the cost of a prolonged labour with requirement of more oxytocin and fetal malpositioning (Howell CJ., 2005), intrathecal narcotics in the form of fentanyl is a better choice since time from initiation of analgesia to complete dilatation was shorter on an average of 90 minutes with less pain and better Apgar scores (Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, et al., 2005). In a meta-analysis, intrathecal opioids would increase pruritus with equal incidence of nausea and similar method of delivery, and in a series of intrathecal bupivacaine plus sufentanil at various dosages produced similar analgesia in all dosages, but increased dosage would produce more side effects (Wong CA, Scavone BM, Loffredi M, Wang WY, Peaceman AM, Ganchiff JN., 2000). In a study comparing intrathecal bupivacaine plus fentanyl compared with pudendal block, the patients had much more satisfaction with pain relief (Pace MC, Aurilio C, Bulletti C, Iannotti M, Passavanti MB, Palagiano A., 2004), and although fentanyl and bupivacaine was sufficient for the procedure, addition of morphine to it increased duration of analgesia (Yeh HM, Chen LK, Shyu MK, Lin CJ, Sun WZ, Wang MJ, et al., 2001). Conclusion: This literature review shows that intrathecal anaesthesia is a procedure of choice where short-term duration of surgery is considered, and of all the agents, fentanyl alone or in combination is still the best agent to be used as evidenced by literature. Until more studies arrive, fentanyl intrathecally despite limitations is not only safe, but effective, satisfying, and better then the other agents in this category. Reference List Babenco HD, Conard PF, Gross JB., (2000). The pharmacodynamic effect of a remifentanil bolus on ventilatory control. 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Van de Velde, M., Teunkens, A., Hanssens, M., Vandermeersch, E., and Verhaeghe, J., (2004). Intrathecal Sufentanil and Fetal Heart Rate Abnormalities: A Double-Blind, Double Placebo-Controlled Trial Comparing Two Forms of Combined Spinal Epidural Analgesia with Epidural Analgesia in Labor. Anesth. Analg.; 98: 1153 - 1159. Volmanen P, Akural EI, Raudaskoski T, et al., (2002). Remifentanil in obstetric analgesia: a dose finding study. Anesth Analg;94(4):913-7. Walldn, J., Thrn, S., and Wattwil, M., (2004). The Delay of Gastric Emptying Induced by Remifentanil Is Not Influenced by Posture. Anesth. Analg.; 99: 429 - 434. Wong CA, Scavone BM, Peaceman AM, McCarthy RJ, Sullivan JT, Diaz NT, et al., (2005). The risk of cesarean delivery with neuraxial analgesia given early versus late in labor. N Engl J Med; 352(7):655-65. Wong CA, Scavone BM, Loffredi M, Wang WY, Peaceman AM, Ganchiff JN., (2000). The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia. Anesthesiology; 92(6): 1553-8. Yeh HM, Chen LK, Shyu MK, Lin CJ, Sun WZ, Wang MJ, et al., (2001). The addition of morphine prolongs fentanyl-bupivacaine spinal analgesia for the relief of labor pain. Anesth Analg; 92(3): 665-8. Read More