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Postoperative analgesia for patients with obstructive sleep apnea syndrome
Seminars in Anesthesia, Perioperative Medicine and Pain (2007) 26, 103-109
Postoperative analgesia for patients with obstructive sleep apnea syndrome Alexander Wolfson, MD, Robert P. Wong, MD, Patricia M. Veloso, MD, and Christopher L. Wu, MD From the Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, Maryland. KEYWORDS: Postoperative pain; Opioid; Epidural; Regional anesthesia; Nonsteroidal antiinflammatory agents; Mortality
Despite recent publication of societal guidelines on the perioperative management of obstructive sleep apnea (OSA) patients, the postoperative management of analgesia for patients with OSA is controversial. There are a number of systemic and regional analgesic techniques which may be used for the management of pain in the patient with a diagnosis of OSA but it is unclear if there are advantages of one agent over another. Although the analgesic options for patients with OSA are similar to the options to other surgical patients (e.g., systemic opioids, systemic non-opioids, and regional analgesic techniques), there is a smaller margin for error and the potential for a higher likelihood of complications in the postoperative period for OSA patients. The choice of postoperative analgesia should be tailored to the individual patient’s need including the type of surgical procedure, co-existing diseases, and location of recovery. Although common sense suggests that the postoperative use of opioids and sedative should be minimized while that for non-opioid agents and regional analgesic techniques should be maximized, there is little randomized data to support these notions. Nevertheless, patients with OSA who undergo surgical procedures should receive regional analgesia and non-opioid agents (e.g., NSAIDs) if there are no contraindications for their use. Further studies are needed to examine the different analgesic regimens on OSA patient outcomes. © 2007 Elsevier Inc. All rights reserved.
The perioperative management of patients with obstructive sleep apnea (OSA) has gained increasing attention over the past decade. Despite recent publication of societal guidelines on the perioperative management of OSA patients,1 the postoperative management of analgesia for patients with OSA is controversial due to the lack of controlled clinical trials. There are a number of systemic and regional analgesic techniques which may be used for the management of pain in the patient with a diagnosis of OSA, but it is unclear whether there are advantages of one agent over another. In fact, a survey of Canadian anesthesiologists
Address reprint requests and correspondence: Christopher Wu, MD, The Johns Hopkins Hospital, Carnegie 280, 600 North Wolfe Street, Baltimore, MD 21287. E-mail: [email protected].
0277-0326/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.sane.2007.03.002
regarding their practices in dealing with patients with OSA found a tremendous amount of variability.2 The aim of this paper is to discuss the pathophysiology of postoperative complications occurring in patients with OSA and the analgesic options available for the management of postoperative pain in patients with OSA.
Postoperative pathophysiology and complications There appears to be a higher incidence of postoperative complications in patients with OSA compared with those without OSA.3 There are several possible pathophysiologies that may be exacerbated in the postoperative period
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in patients with OSA. It is clear that patients with obstructive apnea, which is defined as a pause of more than 10 seconds in breathing during sleep despite continuing respiratory effort,4 and obstructive sleep apnea syndrome (OSAS), which is defined as the occurrence of at least five apneas or hypopneas per hour in association with symptoms attributable to sleep-disordered breathing,4 are at higher risk for airway obstruction during sleep compared with those without OSA. It is possible that the frequency of these obstructive events increases after surgery with a higher frequency for those with more severe OSA.5 Complicating the postoperative management is the fact that many patients who have OSA may not be diagnosed prior to surgery. Recent estimates place the prevalence of OSAS at 5% of the general population and anywhere from 1% to 9% of patients presenting for surgery.4 Although airway obstruction is most likely one of the central events contributing to postoperative complications in patients with OSA, there are other mechanisms, including the disruption of quality and quantity of rapid eye movement (REM) sleep, which indirectly may lead to postoperative complications. In normal, awake individuals, the phasic activity of the pharyngeal muscles prior to inspiration results in their contraction, which resists the negative pressure generated by the diaphragm and prevents collapse of the upper airway. The disruption of REM sleep postoperatively (along with the administration of opioid analgesics) interferes with phasic pharyngeal muscle contraction and may predispose OSA patients to airway obstruction.6 REM sleep may be associated with increased apneas and episodic oxygen desaturations in non-surgical patients primarily as a result of loss of muscle tone.7 In surgical patients, there is a rebound in REM sleep on the second and third night after surgery, which is associated with a higher incidence of hypoxemia.8,9 Nevertheless, the association between postoperative REM sleep disruption and airway obstruction/hypoxemia is unclear, and other data indicate that the respiratory disturbance of OSA is not greatly affected by sleep stage and that, in some patients, REM rebound in the early postoperative period actually improves OSA symptoms.10 Thus, changes in sleep pattern after surgery may be a possible pathogenic factor in the development of episodic hypoxemia and airway obstruction, although further elucidation is needed. In general, patients with OSA are predisposed to a higher incidence of cardiac arrhythmias, myocardial ischemia, cerebrovascular insufficiency, and intracranial hypertension than those without OSA.6 The hypoxemia associated with OSA may predispose OSA patients to mental dysfunction and poor wound healing after surgery.6,11 Both episodic and constant hypoxemias are commonly seen following major surgery, with maximum changes occurring 2-3 days after the operation.9 A strong temporal correlation between episodic hypoxemia and
myocardial ischemia and arrhythmias has been documented in the late postoperative period by several studies.9 In the postoperative period, the hypoxemia is superimposed on the neuroendocrine surgical stress response with increased vascular tone and tachycardia, which may exacerbate late postoperative myocardial ischemia.9 Finally, OSA patients may be at higher risk for hypoxemia during obstructive episodes as many patients with OSA are also obese, one of most common risk factors for OSA. These patients typically have decreased lung volumes and reserves, particularly functional residual capacity, which may exacerbate hypoxemia during airway obstruction especially after thoracic and abdominal procedures.9 Thus, there are a number of related mechanisms that may contribute to the postoperative pathophysiology in patients with OSA.
Options for postoperative analgesia Analgesic options for patients with OSA are similar to the options for all surgical patients. In general, the mainstay of therapeutic options includes systemic opioids, systemic non-opioids, and regional techniques involving perineural and neuraxial local anesthetics or opioids. What separates the OSA patients from those without OSA is the smaller margin for error and the potential for a higher likelihood of complications in the postoperative period.
ASA Task Force: perioperative management of patients with OSA In May 2006, guidelines were published by the American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Obstructive Sleep Apnea.1 Although the consultants made a number of recommendations for the management of postoperative analgesia in patients with OSA, they also acknowledged that the conclusions regarding postoperative analgesic options were based on insufficient literature evaluating the effects of various techniques, the presence of equivocal literature regarding the use of epidural opioids compared with intramuscular or intravenous opioids in reducing respiratory depression, and insufficient literature regarding the addition of a basal infusion to systemic patient-controlled opioids. Nevertheless, the consultants recommended that regional techniques rather than systemic opioids should be used to reduce the likelihood of adverse outcomes in patients at increased perioperative risk from OSA, the exclusion of opioids from neuraxial postoperative analgesia to reduce risks as compared with neuraxial techniques which include opioids, and the use of nonsteroidal anti-inflammatory agents to reduce adverse outcomes through their opioidsparing effect. The consultants were equivocal regarding whether avoiding a basal infusion of opioids in patients at
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increased perioperative risk from OSA reduces the likelihood of adverse outcomes.
Systemic analgesics Non-opioid analgesics In light of the ASA recommendations, the use of nonopioid analgesics is likely to gain popularity. Depending on the extent of surgery and postoperative pain, non-opioid analgesics may be used as the sole analgesic agents in some cases or as an adjuvant agent in conjunction with other modalities in other instances. Below, we discuss a few of the non-opioid medications that have been studies in patients with OSA or that are commonly used. Tramadol Tramadol is a synthetic analogue of codeine which exhibits a central analgesic activity with a low affinity for opioid receptors. Although tramadol has some selectivity for mu receptors, this activity within the central nervous system is quite low; that is, 6000 times lower than that of morphine.12 Tramadol provides analgesia presumably through inhibition of norepinephrine and serotonin reuptake. After oral administration, tramadol demonstrates 68% bioavailability, with peak serum concentrations reached within 2 hours. The recommended daily dose of tramadol is between 50 and 100 mg orally every 4 to 6 hours, with a maximum dose of 400 mg/day; the duration of the analgesic effect after a single oral dose of tramadol 100 mg is about 6 hours. Adverse effects including nausea are dose-dependent and therefore considerably more likely to appear if the loading dose is high. Although respiratory depression is possible with administration of tramadol, it has a much more favorable profile compared with opioids, and in some studies, the respiratory depressant effect of tramadol was similar to that of placebo.13-15 Tramadol does not depress the hypoxic ventilatory response.16 There are few studies examining the postoperative use of tramadol in patients with OSA. Hullett et al. found no significant difference between two groups of children undergoing adenotosillectomy for OSA who were randomized to receive either perioperative tramadol or morphine in a double-blind fashion.17 Although there was no difference in sedation and pain scores up to 6 hours postoperatively between the groups, there were fewer episodes of postoperative desaturations in the tramadol group and an overall trend toward fewer desaturation events.17 Tramadol may provide similar postoperative analgesia compared with morphine in certain instances.18 Tramadol is only available as an oral formulation in North America; however, intravenous formulations are also available in Europe. Clonidine and dexmedetomidine A2-agonists such as clonidine and dexmedetomidate have become central in the quest for analgesics devoid of
105 opioid-like side-effects. These agents, which can be administered in a variety of routes (eg, oral, intravenous, neuraxial), produce primarily central-mediated analgesia by an opioid-independent mechanism. In a study of healthy young adult males, oral clonidine alone produced little respiratory depression and did not significantly potentiate morphine-induced respiratory depression,19 although other data suggest that there may be a prolongation of a fentanylinduced ventilatory depression when used in combination with clonidine.20 Although dexmedetomidine has an eightfold higher affinity for the A2-adrenoceptor than clonidine, dexmedetomidine can only be administered as a continuous intravenous infusion. In humans, dexmedetomidine infusion causes a mild decrease in minute ventilation and an increase in PaCO2; however, these effects are much less pronounced than with opioids and other systemic agents, and are similar to those seen during profound sleep.21 The addition of dexmedetomidine does not appear to worsen the cardiovascular and respiratory depression associated with high-dose opiates in the spontaneously ventilating rat.22 Finally, there are other properties of alpha-2 agonists that may be particularly useful in the treatment of pain in OSA patients. Clonidine has been shown to possess REM-suppressant effects and to improve the level of nocturnal hypoxemia in patients with OSAS.23 In addition, other data suggest that the preoperative administration of clonidine reduces the changes in heart rate and mean arterial pressure without adversely affecting respiratory rates.24 Similar to that seen with tramadol, there are little data examining the use of alpha-2 agonists in patients with OSA. Patients with OSA scheduled for ear–nose–throat surgery were randomized to receive either oral clonidine or placebo preoperatively.25 The clonidine group had significantly lower mean arterial blood pressures, reduced propofol and opioid consumption, and lower pain scores. The apnea and desaturation indices were not different between the groups; however, the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo clonidine group (mean of 76.7% versus 82.4% for the clonidine group), suggesting that the addition of preoperative oral clonidine may reduce the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation.25 In addition, a case report described a morbidly obese patient with several co-morbidities including OSA who underwent bariatric surgery with a continuous dexmedetomidine infusion26; however, it is difficult to draw any conclusions as the patient also received fentanyl and midazolam during the first postoperative night and was kept intubated until the following morning. Nonsteroidal anti-inflammatory agents and acetaminophen Nonsteroidal anti-inflammatory agents (NSAIDs) and acetaminophen are a diverse group of compounds that produce analgesia through the inhibition of both peripheral and central cyclo-oxygenase. NSAIDs and acetaminophen are commonly used adjuvant agents for the management of
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acute postoperative pain. The discovery of two isoforms of cyclo-oxygenase has led to the development of “specific” cyclo-oxygenase 2 (COX-2) inhibitors in an attempt to limit the side effects associated with nonspecific NSAIDs. Studies have shown to provide a similar degree of analgesia to morphine in certain instances.27,28 This class of analgesics may be particularly useful for the management of postoperative pain in patients with OSA as NSAIDs and acetaminophen do not appear to have any direct respiratory depressant effects. Nevertheless, NSAIDs should not be inappropriately used in OSA patients with heart failure and should probably be avoided in these cases.29 Although the ASA guidelines advocate the use of NSAIDs to reduce adverse outcomes through their opioidsparing effect, several meta-analyses on the postoperative use of NSAIDs have not confirmed this assumption.1,30-32 Although the addition of acetaminophen, COX-2 inhibitors, or NSAID resulted in an opioid-sparing effect, this decrease in opioid consumption did not result in a decrease in the opioid-related side effects/adverse events of respiratory depression.30 Another meta-analysis (22 RCTs with 2307 subjects) evaluating the efficacy of NSAIDs also found that the addition of NSAIDs (versus placebo) to IV PCA morphine for postoperative analgesia did not reduce the risk of respiratory depression.31 Finally, a meta-analysis (7 RCTs with 491 subjects) specifically examined the effect of acetaminophen (versus placebo) on morphine-related adverse events in the postoperative patients receiving IV PCA opioid noted that, although the addition of acetaminophen significantly decreased overall opioid usage, the presence of acetaminophen did not reduce the risk of developing any opioidrelated side effect.32 Thus, it appears that, although the perioperative administration of NSAIDs and acetaminophen does result in an opioid-sparing effect postoperatively, there is no evidence from pooled estimates that this decrease in opioid consumption results in a reduced risk for developing the opioid-related side effect/adverse event of respiratory depression.
Opioid analgesics According to the ASA guidelines, the use of systemic opioids should be minimized to reduce the likelihood of adverse outcomes in patients at increased perioperative risk from OSA.1 Patients with OSA are able to relieve their airway obstruction during the awake state by consciously controlling their own breathing efforts. Opioid-induced suppression of wakefulness may lead to subsequent worsening of airway obstruction. Like other agents with sedative properties, opioids may inhibit upper airway and diaphragmatic activity33 and as such, contribute to postoperative airway obstruction particularly in patients with OSA. Several studies have noted an increased sensitivity to opioids and a reduced opioid analgesic requirement in young children with OSA.34,35 The mechanisms behind these findings are not clear; however, it has been speculated that there may be an upregulation of central opioid receptors as a result of
recurrent hypoxemia in children with severe OSA.36 Similarly, a laboratory investigation noted that rats exposed to recurrent hypoxemia during development exhibit increased sensitivity to fentanyl in later life.37 In fact, Waters et al. found that up to 50% of children with OSA who were intubated but breathing spontaneously under inhalational anesthesia developed apnea precipitated by administration of opioids.38 Finally, in a randomized controlled trial comparing the perioperative use of tramadol with morphine, there were fewer episodes of postoperative desaturation in the tramadol group up to 3 hours postoperatively.17 The postoperative administration of opioids has been alleged to be associated with an increased risk for respiratory depression and even death,39 and the studies reviewed do suggest that opioids should be used, if at all, with great caution in the postoperative period in OSA patients.
Regional analgesia ASA guidelines indicate that regional (eg, epidural and peripheral nerve block) analgesic techniques rather than systemic opioids should be used to reduce the likelihood of adverse outcomes in patients at increased perioperative risk from OSA, and when regional techniques are used that opioids should be excluded from these analgesic regimens.1 Despite the apparent rationale for the use of regional analgesic techniques, there is a lack of studies investigating the use of regional techniques specifically for patients with OSA and there are no well-designed prospective trials to affirm the claim that regional anesthesia is associated with fewer respiratory complications for patients with OSA. Although the local anesthetic used in regional techniques, especially continuous epidural or peripheral nerve catheters, can be absorbed systemically, local anesthetics most likely would have minimal impact on airway collapsibility in OSA patients compared with other analgesic options such as opioids. It is not clear whether opioids administered via a regional technique would result in a different rate of respiratory events (eg, respiratory depression or arrest) compared with that administered via another route (eg, systemic); however, there have been case reports of death presumably related to respiratory arrest in OSA patients who had received continuous infusions of epidural fentanyl as part of their epidural analgesic regimen.40 It is well recognized that fentanyl is a lipophilic opioid which can be absorbed systemically even when administered epidurally, and there is no difference in the incidence of nausea, pruritis, urinary retention, or respiratory complications in patients receiving either epidural or intravenous fentanyl as a continuous infusion.41 There are other potential benefits for postoperative regional analgesic techniques. Both epidural and continuous peripheral regional analgesia have been shown to provide superior postoperative analgesia when compared with systemic opioids.42-44 Patients with OSA may be at
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higher risk for postoperative pulmonary complications and the use of thoracic epidural analgesia is associated with a decrease in postoperative pulmonary complications and respiratory failure in meta-analyses.45,46 The majority of these benefits from epidural analgesia were based on use of a local anesthetic-based analgesic regimen.45 In addition, there are systematic data suggesting that epidural analgesia may be associated with a decrease in the risk of postoperative cardiac events, including myocardial infarction and dysrhythmias.46-48 There is insufficient evidence to determine whether continuous peripheral regional analgesic techniques are also associated with a decreased risk in these outcomes. Despite the theoretical advantages of regional analgesic technique using a local anesthetic only regimen, further studies are needed to verify these benefits particularly as they apply to patients with OSA.
Other considerations The options for postoperative analgesia described above should be considered in the context of the clinical situation; that is, other factors such as the type and extent of surgery and location of discharge (eg, inpatient versus outpatient). Considerations related to postoperative analgesia include the type of postoperative monitoring required and the extent of undiagnosed OSA in patients undergoing surgery. Unfortunately, like that previously discussed for analgesic options, there is little solid data in these areas. There is evidence that the type of surgery may play a role in the incidence of complications for patients with OSA. More extensive surgery may require use of more potent analgesics including opioids. In addition, use of regional analgesic techniques may not be feasible or appropriate for certain types of surgery that may be associated with a higher risk of airway complications. This is particularly true with upper airway surgery due to the fact that the airway caliber is reduced by postoperative edema, presence of nasal packs or tubes, or other intraluminal obstruction such as a hematoma. A study of OSA patients undergoing uvulopalatopharyngoplasty showed no statistical improvement in respiratory disturbance indices for the first two postoperative days, despite an improvement at 3 months.49 A retrospective review of children with OSA undergoing adenotonsillectomy found an increased risk for postoperative respiratory complications especially in children younger than 3 years of age who had an obstructive event index of greater than 10.50 In light of these findings, the authors concluded that children undergoing adenotonsillectomy for OSA should be monitored in the hospital in the postoperative period. The ASA guidelines singled out orthopedic surgery as having the lowest risk of perioperative complications for patients with obstructive sleep apnea,1 presumably resulting from the reduced risk from the use of regional analgesic techniques for extremity surgery. However, OSA patients un-
107 dergoing certain orthopedic procedures still have a higher risk of postoperative complications compared with those without OSA.51 The use of potent anticoagulants, such as low molecular weight heparins, may preclude the postoperative use of regional analgesic techniques such as epidural analgesia. Regardless of the type of postoperative analgesic regimen chosen, the need for telemetry monitoring (eg, pulse oximetry, electrocardiogram) postoperatively on the surgical ward in OSA patients is uncertain as is the efficacy of this type of monitoring in minimizing the risk of adverse postoperative events in OSA patients.1 In addition, the impact of monitored postoperative settings (eg, stepdown or intensive care unit) compared with routine hospital wards for patients with known or suspected OSA is uncertain.1 Although patients with OSA may require careful monitoring and vigilance, especially during the first 24 hours after surgery, there is insufficient evidence regarding the appropriate duration of postoperative respiratory monitoring in patients with OSA.1 Several studies have shown that significant complications after upper airway surgery for OSA usually occur in the first 2 hours after surgery.52,53 The decision regarding intensive care, surgical ward, or at home monitoring should ideally be made prior to surgery but may be made in the recovery room.6 Admission to the intensive care unit may not be necessary for patients with OSA even after upper airway surgery.52 The provision of postoperative analgesia for OSA patients undergoing outpatient surgery is particularly challenging, reflecting some of the controversies regarding which patients with OSA can be safely managed on an outpatient (as opposed to an inpatient) basis, and the appropriate time for discharge of these patients following outpatient surgery.1 Although some procedures that are typically performed on an outpatient basis in non-OSA patients may also be safely performed on an outpatient basis in OSA patients when local or regional anesthesia is administered,1 careful consideration should be given to the postoperative analgesic regimen in these patients who will be discharged to home in a relatively unmonitored setting. Use of NSAIDs and acetaminophen should be optimized (prescribed as “around the clock” rather than “as needed”). The use of non-opioid analgesic such as tramadol should be given preference over opioid analgesics. Finally, regional analgesic techniques should be administered both intraoperatively and postoperatively (eg, continuous wound irrigation with local anesthetic via an indwelling catheter or continuous peripheral nerve analgesia at home) if feasible. The use of sedatives in the postoperative setting (for either an inpatient or outpatient basis) should be limited54,55 in an attempt to minimize suppression of respiratory effort and consciousness.
Summary The management of postoperative analgesia in the patient with OSA is extremely challenging for the clinician caring
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for these patients. Although common sense dictates that we should minimize postoperative use of opioids and sedative while maximizing the utilization of non-opioid agents and regional analgesic techniques, there is little randomized data to support these notions. Nevertheless, patients with OSA who undergo surgical procedures should receive regional analgesia and non-opioid agents (eg, NSAIDs, tramadol) if there are no contraindications for their use. Further studies are needed to examine the different analgesic regimens on OSA patient outcomes.
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19. Bailey PL, Sperry RJ, Johnson GK, et al: Respiratory effects of clonidine alone and combined with morphine, in humans. Anesthesiology 74:43-48, 1991 20. Luebbe N, Walz R, Walz K, et al: Clonidine prolongs fentanyl-induced ventilatory depression. Eur J Anaesthesiol 15:292-296, 1998 21. Belleville JP, Ward DS, Bloor BC, et al: Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 77:1125-1133, 1992 22. Furst SR, Weinger MB: Dexmedetomidine, a selective alpha 2-agonist, does not potentiate the cardiorespiratory depression of alfentanil in the rat. Anesthesiology 72:882-888, 1990 23. Issa FG: Effect of clonidine in obstructive sleep apnea. Am Rev Respir Dis 145:435-439, 1992 24. Hall JE, Uhrich TD, Ebert TJ: Sedative, analgesic and cognitive effects of clonidine infusions in humans. Br J Anaesth 86:5-11, 2001 25. Pawlik MT, Hansen E, Waldhauser D, et al: Clonidine premedication in patients with sleep apnea syndrome: a randomized, double-blind, placebo-controlled study. Anesth Analg 101:1374-1380, 2005 26. Hofer RE, Sprung J, Sarr MG, et al: Anesthesia for a patient with morbid obesity using dexmedetomidine without narcotics. Can J Anaesth 52:176-180, 2005 27. O’Hara DA, Fragen RJ, Kinzer M, et al: Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. Clin Pharmacol Ther 41:556-561, 1987 28. Yee JP, Koshiver JE, Allbon C, et al: Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery. Pharmacotherapy 6:253-261, 1986 29. Aronow WS: Heart failure update: treatment of heart failure with a normal left ventricular ejection fraction in the elderly. Geriatrics 61: 16-20, 2006 30. Elia N, Lysakowski C, Tramer MR: Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology 103:1296-1304, 2005 31. Marret E, Kurdi O, Zufferey P, et al: Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology 102:1249-1260, 2005 32. Remy C, Marret E, Bonnet F: Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials. Br J Anaesth 94:505-513, 2005 33. Hillman DR, Platt PR, Eastwood PR: The upper airway during anaesthesia. Br J Anaesth 91:31-39, 2003 34. Brown KA, Laferriere A, Lakheeram I, et al: Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology 105:665-669, 2006 35. Brown KA, Laferriere A, Moss IR: Recurrent hypoxemia in young children with obstructive sleep apnea is associated with reduced opioid requirement for analgesia. Anesthesiology 100:806-810, 2004 36. Koomson A, Morin I, Brouillette R, et al: Children with severe OSAS who have adenotonsillectomy in the morning are less likely to have postoperative desaturation than those operated in the afternoon. Can J Anaesth 51:62-67, 2004 37. Moss IR, Brown KA, Laferriere A: Recurrent hypoxia in rats during development increases subsequent respiratory sensitivity to fentanyl. Anesthesiology 105:715-718, 2006 38. Waters KA, McBrien F, Stewart P, et al: Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol 92:1987-1994, 2002 39. Cullen DJ: Obstructive sleep apnea and postoperative analgesia: a potentially dangerous combination. J Clin Anesth 13:83-85, 2001 40. Ostermeier AM, Roizen MF, Hautkappe M, et al: Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea. Anesth Analg 85:452-460, 1997 41. Loper KA, Ready LB, Downey M, et al: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 70:72-75, 1990
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42. Wu CL, Cohen SR, Richman JM, et al: Efficacy of postoperative patient-controlled and continuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology 103:1079-1088, 2005 43. Block BM, Liu SS, Rowlingson AJ, et al: Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA 290:2455-2463, 2003 44. Richman JM, Liu SS, Courpas G, et al: Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis. Anesth Analg 102:248-257, 2006 45. Ballantyne JC, Carr DB, deFerranti S, et al: The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg 86:598612, 1998 46. Nishimori M, Ballantyne JC, Low JH: Epidural pain relief versus systemic opioid-based pain relief for abdominal aortic surgery. Cochrane Database Syst Rev 3:CD005059, 2006 47. Beattie WS, Badner NH, Choi P: Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis. Anesth Analg 93:853858, 2001 48. Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: a metaanalysis. Anesthesiology 101:153-161, 2004
109 49. Burgess LP, Derderian SS, Morin GV, et al: Postoperative risk following uvulopalatopharyngoplasty for obstructive sleep apnea. Otolaryngol Head Neck Surg 106:81-86, 1992 50. McColley SA, April MM, Carroll JL, et al: Respiratory compromise after adenotonsillectomy in children with obstructive sleep apnea. Arch Otolaryngol Head Neck Surg 118:940-943, 1992 51. Gupta RM, Parvizi J, Hanssen AD, et al: Postoperative complications in patients with obstructive sleep apnea syndrome undergoing hip or knee replacement: a case-control study. Mayo Clin Proc 76:897-905, 2001 52. Terris DJ, Fincher EF, Hanasono MM, et al: Conservation of resources: indications for intensive care monitoring after upper airway surgery on patients with obstructive sleep apnea. Laryngoscope 108: 784-788, 1998 53. Rosenberg J, Rasmussen GI, Wojdemann KR, et al: Ventilatory pattern and associated episodic hypoxaemia in the late postoperative period in the general surgical ward. Anaesthesia 54:323-328, 1999 54. Connolly LA: Anesthetic management of obstructive sleep apnea patients. J Clin Anesth 3:461-469, 1991 55. Warwick JP, Mason DG: Obstructive sleep apnoea syndrome in children. Anaesthesia 53:571-579, 1998
Postoperative analgesia for patients with obstructive sleep apnea syndrome Alexander Wolfson, MD, Robert P. Wong, MD, Patricia M. Veloso, MD, and Christopher L. Wu, MD From the Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, Maryland. KEYWORDS: Postoperative pain; Opioid; Epidural; Regional anesthesia; Nonsteroidal antiinflammatory agents; Mortality
Despite recent publication of societal guidelines on the perioperative management of obstructive sleep apnea (OSA) patients, the postoperative management of analgesia for patients with OSA is controversial. There are a number of systemic and regional analgesic techniques which may be used for the management of pain in the patient with a diagnosis of OSA but it is unclear if there are advantages of one agent over another. Although the analgesic options for patients with OSA are similar to the options to other surgical patients (e.g., systemic opioids, systemic non-opioids, and regional analgesic techniques), there is a smaller margin for error and the potential for a higher likelihood of complications in the postoperative period for OSA patients. The choice of postoperative analgesia should be tailored to the individual patient’s need including the type of surgical procedure, co-existing diseases, and location of recovery. Although common sense suggests that the postoperative use of opioids and sedative should be minimized while that for non-opioid agents and regional analgesic techniques should be maximized, there is little randomized data to support these notions. Nevertheless, patients with OSA who undergo surgical procedures should receive regional analgesia and non-opioid agents (e.g., NSAIDs) if there are no contraindications for their use. Further studies are needed to examine the different analgesic regimens on OSA patient outcomes. © 2007 Elsevier Inc. All rights reserved.
The perioperative management of patients with obstructive sleep apnea (OSA) has gained increasing attention over the past decade. Despite recent publication of societal guidelines on the perioperative management of OSA patients,1 the postoperative management of analgesia for patients with OSA is controversial due to the lack of controlled clinical trials. There are a number of systemic and regional analgesic techniques which may be used for the management of pain in the patient with a diagnosis of OSA, but it is unclear whether there are advantages of one agent over another. In fact, a survey of Canadian anesthesiologists
Address reprint requests and correspondence: Christopher Wu, MD, The Johns Hopkins Hospital, Carnegie 280, 600 North Wolfe Street, Baltimore, MD 21287. E-mail: [email protected].
0277-0326/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.sane.2007.03.002
regarding their practices in dealing with patients with OSA found a tremendous amount of variability.2 The aim of this paper is to discuss the pathophysiology of postoperative complications occurring in patients with OSA and the analgesic options available for the management of postoperative pain in patients with OSA.
Postoperative pathophysiology and complications There appears to be a higher incidence of postoperative complications in patients with OSA compared with those without OSA.3 There are several possible pathophysiologies that may be exacerbated in the postoperative period
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in patients with OSA. It is clear that patients with obstructive apnea, which is defined as a pause of more than 10 seconds in breathing during sleep despite continuing respiratory effort,4 and obstructive sleep apnea syndrome (OSAS), which is defined as the occurrence of at least five apneas or hypopneas per hour in association with symptoms attributable to sleep-disordered breathing,4 are at higher risk for airway obstruction during sleep compared with those without OSA. It is possible that the frequency of these obstructive events increases after surgery with a higher frequency for those with more severe OSA.5 Complicating the postoperative management is the fact that many patients who have OSA may not be diagnosed prior to surgery. Recent estimates place the prevalence of OSAS at 5% of the general population and anywhere from 1% to 9% of patients presenting for surgery.4 Although airway obstruction is most likely one of the central events contributing to postoperative complications in patients with OSA, there are other mechanisms, including the disruption of quality and quantity of rapid eye movement (REM) sleep, which indirectly may lead to postoperative complications. In normal, awake individuals, the phasic activity of the pharyngeal muscles prior to inspiration results in their contraction, which resists the negative pressure generated by the diaphragm and prevents collapse of the upper airway. The disruption of REM sleep postoperatively (along with the administration of opioid analgesics) interferes with phasic pharyngeal muscle contraction and may predispose OSA patients to airway obstruction.6 REM sleep may be associated with increased apneas and episodic oxygen desaturations in non-surgical patients primarily as a result of loss of muscle tone.7 In surgical patients, there is a rebound in REM sleep on the second and third night after surgery, which is associated with a higher incidence of hypoxemia.8,9 Nevertheless, the association between postoperative REM sleep disruption and airway obstruction/hypoxemia is unclear, and other data indicate that the respiratory disturbance of OSA is not greatly affected by sleep stage and that, in some patients, REM rebound in the early postoperative period actually improves OSA symptoms.10 Thus, changes in sleep pattern after surgery may be a possible pathogenic factor in the development of episodic hypoxemia and airway obstruction, although further elucidation is needed. In general, patients with OSA are predisposed to a higher incidence of cardiac arrhythmias, myocardial ischemia, cerebrovascular insufficiency, and intracranial hypertension than those without OSA.6 The hypoxemia associated with OSA may predispose OSA patients to mental dysfunction and poor wound healing after surgery.6,11 Both episodic and constant hypoxemias are commonly seen following major surgery, with maximum changes occurring 2-3 days after the operation.9 A strong temporal correlation between episodic hypoxemia and
myocardial ischemia and arrhythmias has been documented in the late postoperative period by several studies.9 In the postoperative period, the hypoxemia is superimposed on the neuroendocrine surgical stress response with increased vascular tone and tachycardia, which may exacerbate late postoperative myocardial ischemia.9 Finally, OSA patients may be at higher risk for hypoxemia during obstructive episodes as many patients with OSA are also obese, one of most common risk factors for OSA. These patients typically have decreased lung volumes and reserves, particularly functional residual capacity, which may exacerbate hypoxemia during airway obstruction especially after thoracic and abdominal procedures.9 Thus, there are a number of related mechanisms that may contribute to the postoperative pathophysiology in patients with OSA.
Options for postoperative analgesia Analgesic options for patients with OSA are similar to the options for all surgical patients. In general, the mainstay of therapeutic options includes systemic opioids, systemic non-opioids, and regional techniques involving perineural and neuraxial local anesthetics or opioids. What separates the OSA patients from those without OSA is the smaller margin for error and the potential for a higher likelihood of complications in the postoperative period.
ASA Task Force: perioperative management of patients with OSA In May 2006, guidelines were published by the American Society of Anesthesiologists Task Force on Perioperative Management of Patients with Obstructive Sleep Apnea.1 Although the consultants made a number of recommendations for the management of postoperative analgesia in patients with OSA, they also acknowledged that the conclusions regarding postoperative analgesic options were based on insufficient literature evaluating the effects of various techniques, the presence of equivocal literature regarding the use of epidural opioids compared with intramuscular or intravenous opioids in reducing respiratory depression, and insufficient literature regarding the addition of a basal infusion to systemic patient-controlled opioids. Nevertheless, the consultants recommended that regional techniques rather than systemic opioids should be used to reduce the likelihood of adverse outcomes in patients at increased perioperative risk from OSA, the exclusion of opioids from neuraxial postoperative analgesia to reduce risks as compared with neuraxial techniques which include opioids, and the use of nonsteroidal anti-inflammatory agents to reduce adverse outcomes through their opioidsparing effect. The consultants were equivocal regarding whether avoiding a basal infusion of opioids in patients at
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increased perioperative risk from OSA reduces the likelihood of adverse outcomes.
Systemic analgesics Non-opioid analgesics In light of the ASA recommendations, the use of nonopioid analgesics is likely to gain popularity. Depending on the extent of surgery and postoperative pain, non-opioid analgesics may be used as the sole analgesic agents in some cases or as an adjuvant agent in conjunction with other modalities in other instances. Below, we discuss a few of the non-opioid medications that have been studies in patients with OSA or that are commonly used. Tramadol Tramadol is a synthetic analogue of codeine which exhibits a central analgesic activity with a low affinity for opioid receptors. Although tramadol has some selectivity for mu receptors, this activity within the central nervous system is quite low; that is, 6000 times lower than that of morphine.12 Tramadol provides analgesia presumably through inhibition of norepinephrine and serotonin reuptake. After oral administration, tramadol demonstrates 68% bioavailability, with peak serum concentrations reached within 2 hours. The recommended daily dose of tramadol is between 50 and 100 mg orally every 4 to 6 hours, with a maximum dose of 400 mg/day; the duration of the analgesic effect after a single oral dose of tramadol 100 mg is about 6 hours. Adverse effects including nausea are dose-dependent and therefore considerably more likely to appear if the loading dose is high. Although respiratory depression is possible with administration of tramadol, it has a much more favorable profile compared with opioids, and in some studies, the respiratory depressant effect of tramadol was similar to that of placebo.13-15 Tramadol does not depress the hypoxic ventilatory response.16 There are few studies examining the postoperative use of tramadol in patients with OSA. Hullett et al. found no significant difference between two groups of children undergoing adenotosillectomy for OSA who were randomized to receive either perioperative tramadol or morphine in a double-blind fashion.17 Although there was no difference in sedation and pain scores up to 6 hours postoperatively between the groups, there were fewer episodes of postoperative desaturations in the tramadol group and an overall trend toward fewer desaturation events.17 Tramadol may provide similar postoperative analgesia compared with morphine in certain instances.18 Tramadol is only available as an oral formulation in North America; however, intravenous formulations are also available in Europe. Clonidine and dexmedetomidine A2-agonists such as clonidine and dexmedetomidate have become central in the quest for analgesics devoid of
105 opioid-like side-effects. These agents, which can be administered in a variety of routes (eg, oral, intravenous, neuraxial), produce primarily central-mediated analgesia by an opioid-independent mechanism. In a study of healthy young adult males, oral clonidine alone produced little respiratory depression and did not significantly potentiate morphine-induced respiratory depression,19 although other data suggest that there may be a prolongation of a fentanylinduced ventilatory depression when used in combination with clonidine.20 Although dexmedetomidine has an eightfold higher affinity for the A2-adrenoceptor than clonidine, dexmedetomidine can only be administered as a continuous intravenous infusion. In humans, dexmedetomidine infusion causes a mild decrease in minute ventilation and an increase in PaCO2; however, these effects are much less pronounced than with opioids and other systemic agents, and are similar to those seen during profound sleep.21 The addition of dexmedetomidine does not appear to worsen the cardiovascular and respiratory depression associated with high-dose opiates in the spontaneously ventilating rat.22 Finally, there are other properties of alpha-2 agonists that may be particularly useful in the treatment of pain in OSA patients. Clonidine has been shown to possess REM-suppressant effects and to improve the level of nocturnal hypoxemia in patients with OSAS.23 In addition, other data suggest that the preoperative administration of clonidine reduces the changes in heart rate and mean arterial pressure without adversely affecting respiratory rates.24 Similar to that seen with tramadol, there are little data examining the use of alpha-2 agonists in patients with OSA. Patients with OSA scheduled for ear–nose–throat surgery were randomized to receive either oral clonidine or placebo preoperatively.25 The clonidine group had significantly lower mean arterial blood pressures, reduced propofol and opioid consumption, and lower pain scores. The apnea and desaturation indices were not different between the groups; however, the minimal postoperative oxygen saturation on the day of surgery was significantly lower in the placebo clonidine group (mean of 76.7% versus 82.4% for the clonidine group), suggesting that the addition of preoperative oral clonidine may reduce the amount of intraoperative anesthetics and postoperative opioids without deterioration of ventilation.25 In addition, a case report described a morbidly obese patient with several co-morbidities including OSA who underwent bariatric surgery with a continuous dexmedetomidine infusion26; however, it is difficult to draw any conclusions as the patient also received fentanyl and midazolam during the first postoperative night and was kept intubated until the following morning. Nonsteroidal anti-inflammatory agents and acetaminophen Nonsteroidal anti-inflammatory agents (NSAIDs) and acetaminophen are a diverse group of compounds that produce analgesia through the inhibition of both peripheral and central cyclo-oxygenase. NSAIDs and acetaminophen are commonly used adjuvant agents for the management of
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acute postoperative pain. The discovery of two isoforms of cyclo-oxygenase has led to the development of “specific” cyclo-oxygenase 2 (COX-2) inhibitors in an attempt to limit the side effects associated with nonspecific NSAIDs. Studies have shown to provide a similar degree of analgesia to morphine in certain instances.27,28 This class of analgesics may be particularly useful for the management of postoperative pain in patients with OSA as NSAIDs and acetaminophen do not appear to have any direct respiratory depressant effects. Nevertheless, NSAIDs should not be inappropriately used in OSA patients with heart failure and should probably be avoided in these cases.29 Although the ASA guidelines advocate the use of NSAIDs to reduce adverse outcomes through their opioidsparing effect, several meta-analyses on the postoperative use of NSAIDs have not confirmed this assumption.1,30-32 Although the addition of acetaminophen, COX-2 inhibitors, or NSAID resulted in an opioid-sparing effect, this decrease in opioid consumption did not result in a decrease in the opioid-related side effects/adverse events of respiratory depression.30 Another meta-analysis (22 RCTs with 2307 subjects) evaluating the efficacy of NSAIDs also found that the addition of NSAIDs (versus placebo) to IV PCA morphine for postoperative analgesia did not reduce the risk of respiratory depression.31 Finally, a meta-analysis (7 RCTs with 491 subjects) specifically examined the effect of acetaminophen (versus placebo) on morphine-related adverse events in the postoperative patients receiving IV PCA opioid noted that, although the addition of acetaminophen significantly decreased overall opioid usage, the presence of acetaminophen did not reduce the risk of developing any opioidrelated side effect.32 Thus, it appears that, although the perioperative administration of NSAIDs and acetaminophen does result in an opioid-sparing effect postoperatively, there is no evidence from pooled estimates that this decrease in opioid consumption results in a reduced risk for developing the opioid-related side effect/adverse event of respiratory depression.
Opioid analgesics According to the ASA guidelines, the use of systemic opioids should be minimized to reduce the likelihood of adverse outcomes in patients at increased perioperative risk from OSA.1 Patients with OSA are able to relieve their airway obstruction during the awake state by consciously controlling their own breathing efforts. Opioid-induced suppression of wakefulness may lead to subsequent worsening of airway obstruction. Like other agents with sedative properties, opioids may inhibit upper airway and diaphragmatic activity33 and as such, contribute to postoperative airway obstruction particularly in patients with OSA. Several studies have noted an increased sensitivity to opioids and a reduced opioid analgesic requirement in young children with OSA.34,35 The mechanisms behind these findings are not clear; however, it has been speculated that there may be an upregulation of central opioid receptors as a result of
recurrent hypoxemia in children with severe OSA.36 Similarly, a laboratory investigation noted that rats exposed to recurrent hypoxemia during development exhibit increased sensitivity to fentanyl in later life.37 In fact, Waters et al. found that up to 50% of children with OSA who were intubated but breathing spontaneously under inhalational anesthesia developed apnea precipitated by administration of opioids.38 Finally, in a randomized controlled trial comparing the perioperative use of tramadol with morphine, there were fewer episodes of postoperative desaturation in the tramadol group up to 3 hours postoperatively.17 The postoperative administration of opioids has been alleged to be associated with an increased risk for respiratory depression and even death,39 and the studies reviewed do suggest that opioids should be used, if at all, with great caution in the postoperative period in OSA patients.
Regional analgesia ASA guidelines indicate that regional (eg, epidural and peripheral nerve block) analgesic techniques rather than systemic opioids should be used to reduce the likelihood of adverse outcomes in patients at increased perioperative risk from OSA, and when regional techniques are used that opioids should be excluded from these analgesic regimens.1 Despite the apparent rationale for the use of regional analgesic techniques, there is a lack of studies investigating the use of regional techniques specifically for patients with OSA and there are no well-designed prospective trials to affirm the claim that regional anesthesia is associated with fewer respiratory complications for patients with OSA. Although the local anesthetic used in regional techniques, especially continuous epidural or peripheral nerve catheters, can be absorbed systemically, local anesthetics most likely would have minimal impact on airway collapsibility in OSA patients compared with other analgesic options such as opioids. It is not clear whether opioids administered via a regional technique would result in a different rate of respiratory events (eg, respiratory depression or arrest) compared with that administered via another route (eg, systemic); however, there have been case reports of death presumably related to respiratory arrest in OSA patients who had received continuous infusions of epidural fentanyl as part of their epidural analgesic regimen.40 It is well recognized that fentanyl is a lipophilic opioid which can be absorbed systemically even when administered epidurally, and there is no difference in the incidence of nausea, pruritis, urinary retention, or respiratory complications in patients receiving either epidural or intravenous fentanyl as a continuous infusion.41 There are other potential benefits for postoperative regional analgesic techniques. Both epidural and continuous peripheral regional analgesia have been shown to provide superior postoperative analgesia when compared with systemic opioids.42-44 Patients with OSA may be at
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higher risk for postoperative pulmonary complications and the use of thoracic epidural analgesia is associated with a decrease in postoperative pulmonary complications and respiratory failure in meta-analyses.45,46 The majority of these benefits from epidural analgesia were based on use of a local anesthetic-based analgesic regimen.45 In addition, there are systematic data suggesting that epidural analgesia may be associated with a decrease in the risk of postoperative cardiac events, including myocardial infarction and dysrhythmias.46-48 There is insufficient evidence to determine whether continuous peripheral regional analgesic techniques are also associated with a decreased risk in these outcomes. Despite the theoretical advantages of regional analgesic technique using a local anesthetic only regimen, further studies are needed to verify these benefits particularly as they apply to patients with OSA.
Other considerations The options for postoperative analgesia described above should be considered in the context of the clinical situation; that is, other factors such as the type and extent of surgery and location of discharge (eg, inpatient versus outpatient). Considerations related to postoperative analgesia include the type of postoperative monitoring required and the extent of undiagnosed OSA in patients undergoing surgery. Unfortunately, like that previously discussed for analgesic options, there is little solid data in these areas. There is evidence that the type of surgery may play a role in the incidence of complications for patients with OSA. More extensive surgery may require use of more potent analgesics including opioids. In addition, use of regional analgesic techniques may not be feasible or appropriate for certain types of surgery that may be associated with a higher risk of airway complications. This is particularly true with upper airway surgery due to the fact that the airway caliber is reduced by postoperative edema, presence of nasal packs or tubes, or other intraluminal obstruction such as a hematoma. A study of OSA patients undergoing uvulopalatopharyngoplasty showed no statistical improvement in respiratory disturbance indices for the first two postoperative days, despite an improvement at 3 months.49 A retrospective review of children with OSA undergoing adenotonsillectomy found an increased risk for postoperative respiratory complications especially in children younger than 3 years of age who had an obstructive event index of greater than 10.50 In light of these findings, the authors concluded that children undergoing adenotonsillectomy for OSA should be monitored in the hospital in the postoperative period. The ASA guidelines singled out orthopedic surgery as having the lowest risk of perioperative complications for patients with obstructive sleep apnea,1 presumably resulting from the reduced risk from the use of regional analgesic techniques for extremity surgery. However, OSA patients un-
107 dergoing certain orthopedic procedures still have a higher risk of postoperative complications compared with those without OSA.51 The use of potent anticoagulants, such as low molecular weight heparins, may preclude the postoperative use of regional analgesic techniques such as epidural analgesia. Regardless of the type of postoperative analgesic regimen chosen, the need for telemetry monitoring (eg, pulse oximetry, electrocardiogram) postoperatively on the surgical ward in OSA patients is uncertain as is the efficacy of this type of monitoring in minimizing the risk of adverse postoperative events in OSA patients.1 In addition, the impact of monitored postoperative settings (eg, stepdown or intensive care unit) compared with routine hospital wards for patients with known or suspected OSA is uncertain.1 Although patients with OSA may require careful monitoring and vigilance, especially during the first 24 hours after surgery, there is insufficient evidence regarding the appropriate duration of postoperative respiratory monitoring in patients with OSA.1 Several studies have shown that significant complications after upper airway surgery for OSA usually occur in the first 2 hours after surgery.52,53 The decision regarding intensive care, surgical ward, or at home monitoring should ideally be made prior to surgery but may be made in the recovery room.6 Admission to the intensive care unit may not be necessary for patients with OSA even after upper airway surgery.52 The provision of postoperative analgesia for OSA patients undergoing outpatient surgery is particularly challenging, reflecting some of the controversies regarding which patients with OSA can be safely managed on an outpatient (as opposed to an inpatient) basis, and the appropriate time for discharge of these patients following outpatient surgery.1 Although some procedures that are typically performed on an outpatient basis in non-OSA patients may also be safely performed on an outpatient basis in OSA patients when local or regional anesthesia is administered,1 careful consideration should be given to the postoperative analgesic regimen in these patients who will be discharged to home in a relatively unmonitored setting. Use of NSAIDs and acetaminophen should be optimized (prescribed as “around the clock” rather than “as needed”). The use of non-opioid analgesic such as tramadol should be given preference over opioid analgesics. Finally, regional analgesic techniques should be administered both intraoperatively and postoperatively (eg, continuous wound irrigation with local anesthetic via an indwelling catheter or continuous peripheral nerve analgesia at home) if feasible. The use of sedatives in the postoperative setting (for either an inpatient or outpatient basis) should be limited54,55 in an attempt to minimize suppression of respiratory effort and consciousness.
Summary The management of postoperative analgesia in the patient with OSA is extremely challenging for the clinician caring
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for these patients. Although common sense dictates that we should minimize postoperative use of opioids and sedative while maximizing the utilization of non-opioid agents and regional analgesic techniques, there is little randomized data to support these notions. Nevertheless, patients with OSA who undergo surgical procedures should receive regional analgesia and non-opioid agents (eg, NSAIDs, tramadol) if there are no contraindications for their use. Further studies are needed to examine the different analgesic regimens on OSA patient outcomes.
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19. Bailey PL, Sperry RJ, Johnson GK, et al: Respiratory effects of clonidine alone and combined with morphine, in humans. Anesthesiology 74:43-48, 1991 20. Luebbe N, Walz R, Walz K, et al: Clonidine prolongs fentanyl-induced ventilatory depression. Eur J Anaesthesiol 15:292-296, 1998 21. Belleville JP, Ward DS, Bloor BC, et al: Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate. Anesthesiology 77:1125-1133, 1992 22. Furst SR, Weinger MB: Dexmedetomidine, a selective alpha 2-agonist, does not potentiate the cardiorespiratory depression of alfentanil in the rat. Anesthesiology 72:882-888, 1990 23. Issa FG: Effect of clonidine in obstructive sleep apnea. Am Rev Respir Dis 145:435-439, 1992 24. Hall JE, Uhrich TD, Ebert TJ: Sedative, analgesic and cognitive effects of clonidine infusions in humans. Br J Anaesth 86:5-11, 2001 25. Pawlik MT, Hansen E, Waldhauser D, et al: Clonidine premedication in patients with sleep apnea syndrome: a randomized, double-blind, placebo-controlled study. Anesth Analg 101:1374-1380, 2005 26. Hofer RE, Sprung J, Sarr MG, et al: Anesthesia for a patient with morbid obesity using dexmedetomidine without narcotics. Can J Anaesth 52:176-180, 2005 27. O’Hara DA, Fragen RJ, Kinzer M, et al: Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain. Clin Pharmacol Ther 41:556-561, 1987 28. Yee JP, Koshiver JE, Allbon C, et al: Comparison of intramuscular ketorolac tromethamine and morphine sulfate for analgesia of pain after major surgery. Pharmacotherapy 6:253-261, 1986 29. Aronow WS: Heart failure update: treatment of heart failure with a normal left ventricular ejection fraction in the elderly. Geriatrics 61: 16-20, 2006 30. Elia N, Lysakowski C, Tramer MR: Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology 103:1296-1304, 2005 31. Marret E, Kurdi O, Zufferey P, et al: Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology 102:1249-1260, 2005 32. Remy C, Marret E, Bonnet F: Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials. Br J Anaesth 94:505-513, 2005 33. Hillman DR, Platt PR, Eastwood PR: The upper airway during anaesthesia. Br J Anaesth 91:31-39, 2003 34. Brown KA, Laferriere A, Lakheeram I, et al: Recurrent hypoxemia in children is associated with increased analgesic sensitivity to opiates. Anesthesiology 105:665-669, 2006 35. Brown KA, Laferriere A, Moss IR: Recurrent hypoxemia in young children with obstructive sleep apnea is associated with reduced opioid requirement for analgesia. Anesthesiology 100:806-810, 2004 36. Koomson A, Morin I, Brouillette R, et al: Children with severe OSAS who have adenotonsillectomy in the morning are less likely to have postoperative desaturation than those operated in the afternoon. Can J Anaesth 51:62-67, 2004 37. Moss IR, Brown KA, Laferriere A: Recurrent hypoxia in rats during development increases subsequent respiratory sensitivity to fentanyl. Anesthesiology 105:715-718, 2006 38. Waters KA, McBrien F, Stewart P, et al: Effects of OSA, inhalational anesthesia, and fentanyl on the airway and ventilation of children. J Appl Physiol 92:1987-1994, 2002 39. Cullen DJ: Obstructive sleep apnea and postoperative analgesia: a potentially dangerous combination. J Clin Anesth 13:83-85, 2001 40. Ostermeier AM, Roizen MF, Hautkappe M, et al: Three sudden postoperative respiratory arrests associated with epidural opioids in patients with sleep apnea. Anesth Analg 85:452-460, 1997 41. Loper KA, Ready LB, Downey M, et al: Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 70:72-75, 1990
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