''what's new in obstetric anesthesia'' lecture reviews literature. Labor analgesia, post-cesarean delivery and preeclampsia are covered. Labor pain is a clinical model for studying acute pain.
''what's new in obstetric anesthesia'' lecture reviews literature. Labor analgesia, post-cesarean delivery and preeclampsia are covered. Labor pain is a clinical model for studying acute pain.
''what's new in obstetric anesthesia'' lecture reviews literature. Labor analgesia, post-cesarean delivery and preeclampsia are covered. Labor pain is a clinical model for studying acute pain.
Ruth Landau Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, Seattle, Washington, USA Introduction Labor analgesia Post-cesarean delivery analgesia Post-preeclampsia outcomes Conclusions References Introduction For over three decades, one of the highlights of the an- nual meeting of the Society for Obstetric Anesthesia and Perinatology has been the Whats New in Obstetric Anesthesia lecture. This lecture, renamed in honor of Gerard W. Ostheimer, MD in 1995, reviews the preced- ing years literature relevant to the practice of obstetric anesthesia. This article, which is the result of reviewing over 1400 scientic manuscripts to create the 2008 Ostheimer lecture, focuses on three key areas: recent advances in labor analgesia, post-cesarean delivery analgesia and novel developments surrounding the long- term outcomes of preeclampsia. Labor analgesia Since the rst description of intrathecal cocaine to pro- vide labor analgesia by Oskar Kreis in 1900, 1 advances in neuraxial pharmacology and technology have pro- vided opportunities to expand and improve labor analgesia. The International Association for the Study of Pain (IASP) declared 2007-2008 as the Global Year Against Pain in Women Real Women, Real Pain. 2 Key points presented in their report relate to: (1) the importance of treating pain within the pregnant population and the substantial public health impact if pain is neglected; (2) the alarmingly high rate of acute or chronic pain after delivery (70%); and (3) labor pain as a clinical model for studying acute pain. In recent years there has been interest in evaluating pain and pain relief accurately, due to the subjective nat- ure of the outcome parameters, signicant inter-individ- ual variability in pain perception and the complexity of womens overall experience during labor and delivery. Ohel et al. 3 prospectively tested nulliparous and multi- parous women at term for the presence of endogenous analgesia during the peripartum period. Using a dolo- rimeter, a pressure algometer applied on different points on the body to determine pressure pain thresholds, the authors found an increase in pain threshold during ac- tive labor compared with an evaluation before labor. They concluded that this threshold increase might have a protective effect during the intense experience of labor pain. Further directions in research may test the hypothesis that increased pain thresholds and enhanced endoge- nous opioids in pregnant women before or during labor may reduce labor analgesic requirements. If conrmed, this may translate into clinically relevant outcomes such as the provision of neuraxial analgesia at later stages in Accepted April 2009 The 2008 Gerard W. Ostheimer Lecture. Given at the Annual Meeting of the Society for Obstetric Anesthesia and Perinatology, Chicago, IL, 2008. Correspondence to: Ruth Landau, MD, Virginia and Prentice Bloedel Professor of Anesthesiology, Director of Obstetric Anesthesia and Clinical Genetics Research, Department of Anesthesiology and Pain Medicine, University of Washington Medical Center, 1959 NE Pacic Street, Suite BB 1415C, Seattle, WA 98195-6540, USA. Tel.: +1 206 543 2187. E-mail address: rulandau@u.washington.edu International Journal of Obstetric Anesthesia (2009) 18, 368372 0959-289X/$ - see front matter
c 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.ijoa.2009.04.009 www.obstetanesthesia.com labor, effective labor or post-cesarean analgesia with reduced doses of analgesic agents, and improved long- term postpartum outcomes. Provision of effective and safe labor analgesia re- mains an ongoing challenge as demonstrated by the number of studies investigating the selection of local anesthetic agents, optimal doses, and location for depo- sition (for example, the epidural or intrathecal space), as well as the modalities used for their administration. Lyons et al. 4 postulated that reducing the concentration of local anesthetic agents with the aim of reducing tox- icity and motor blockade might not necessarily require increasing the dose in a linear manner to provide effec- tive epidural labor analgesia. Using an up-down sequen- tial allocation method, the authors sought to determine the minimum local analgesic volume (MLAV) and min- imum local analgesic dose (MLAD) of an initial bolus of epidural bupivacaine 0.125% and 0.25%. MLAV of bupivacaine 0.125% was 13.6 mL (95% CI 12.414.8) versus 9.2 mL (95% CI 6.911.5) for bupivacaine 0.25% (P = 0.002). Hence, by reducing concentration, equivalent labor analgesia was achieved with a signi- cant reduction in dose of bupivacaine. Such reductions in dose without compromising analgesic efcacy provide a greater margin of safety and allow ne-tuning of labor analgesia. These results are important from both a phar- macologic and a clinical perspective; similar future stud- ies could determine the optimal volume of bupivacaine as an epidural top-up for breakthrough pain at later stages of labor. Recent studies have examined the motor blocking effects of local anesthetic agents and the subsequent impact on mode of delivery. Beilin et al. 5 studied low concentrations of epidural local anesthetics (0.0625%) for maintenance of labor analgesia and determined that bupivacaine was optimal relative to ropivacaine and lev- obupivacaine in providing effective and cost-efcient analgesia with minor and inconsequential degrees of mo- tor blockade. Van de Velde et al. 6 performed a large ran- domized clinical trial to determine the potency hierarchy of intrathecal bupivacaine, ropivacaine and levobupiva- caine at clinically relevant doses combined with opioids. In this full dose-response study dening the ED95 of all three local anesthetics for intrathecal labor analgesia, there appeared to be little or no benet to the substitution of racemic bupivacaine with ropivacaine or levobupiva- caine in combination with sufentanil when performing a combined-spinal epidural (CSE) technique. Finally, past studies have shown that CSE and low- dose infusions with patient controlled epidural analgesia (PCEA) are exceptional tools for improving patient sat- isfaction with labor analgesia. Women appear to prefer the option of controlling their pain with a push button. However, there is no consensus on the optimal program for PCEA labor analgesia. One of the more interesting recent concepts relates to the paradigm that large bo- luses of diluted epidural solutions, rather than a contin- uous infusion of the same amount of local anesthetics, may provide better spread of the infusate and therefore better sensory blockade. Recent studies using various PCEA pump prototypes with computerized algo- rithms 79 appear to conrm that these innovative drug delivery methods achieve better analgesia and patient satisfaction throughout labor with overall lower amounts of local anesthetic agent. Sia et al. 10 demon- strated that high-tech PCEA pumps with automated mandatory boluses compared with basal continuous infusions of local anesthetic agents and opioids (ropiva- caine 0.1% with fentanyl 2 lg/mL; automated 5 mL boluses 1/h versus a basal infusion of 5 mL/h with additional 5 mL PCEA boluses) following an initial spinal analgesic dose resulted in a reduction in total local anesthetic consumption. Whether these prototype pumps and sophisticated drug-delivery systems nd their way into routine clinical practice and further improve maternal labor analgesia remains to be determined. Post-cesarean delivery analgesia The growing increase in rates of cesarean delivery 11 and evidence that severe acute postoperative pain may result in chronic, incapacitating pain after surgery, 12 remind obstetric anesthesiologists that post-cesarean analgesia must be optimized to improve short- and long-term outcomes. Several studies have examined novel ways to provide optimal analgesia following neuraxial anesthesia for cesarean delivery. Carvalho et al. 13,14 conducted two studies looking at the effects of an extended-release epi- dural morphine (EREM) formulation for post-cesarean analgesia. In their second randomized clinical trial, they compared EREM 10 mg with epidural morphine 4 mg in a setting reecting current postoperative obstetric multi- modal analgesia protocols. 14 The authors found a signif- icant morphine-sparing effect between 24 and 48 h after delivery, with superior functional activity in the EREM group. The incidence of side effects and respiratory depression were similar in the two groups. Despite the initial excitement generated by liposomal drug delivery, EREM might not be the panacea for post-cesarean anal- gesia and requires more research to dene its benets. Whether EREM justies using the CSE technique to allow its delivery in the epidural space rather than performing single-shot spinals for elective cesarean deliveries is unknown. Lastly, the concern of inadvertent administration of EREM in the subarachnoid space remains to be resolved. Another novel strategy to optimize post-cesarean analgesia is the intra-wound infusion of non-steroidal anti-inammatory drugs (NSAIDs). Lavandhomme et al. 15 tested the hypothesis that diclofenac has periph- R. Landau 369 eral analgesic properties, in addition to systemic effects, that could reduce local expression of mediators that sensitize nociceptors. In their clinical trial, women scheduled for cesarean delivery under spinal anesthesia were randomized to one of three groups: (1) intra- wound infusion of diclofenac (300 mg/48 h) with an elastomeric pump connected to a multi-hole 20-gauge catheter (Pain Buster; I-Flow Corporation, Lake For- est, CA) inserted supercial to the fascia; (2) intra- wound infusion of ropivacaine 0.2% (5 mL/h for 48 h) with i.v. diclofenac (4 75 mg over 48 h); or (3) intra- wound saline infusion with i.v. diclofenac (4 75 mg over 48 h). Continuous intra-wound infusion of diclo- fenac resulted in greater opioid-sparing and better post- operative analgesia than the same dose administered as an intermittent i.v. bolus, and produced similar analge- sia to the ropivacaine infusion with i.v. diclofenac. There was no apparent benet of either solution beyond 24 h, and the study was underpowered to detect long-term benets. Nonetheless, the overall rate of persistent pain at six months post-cesarean was 14%. These ndings are consistent with other studies suggesting that 7 to 15% of women suffer moderate to severe chronic pain after cesarean deliveries with impaired daily activities. 12,1619 Post-preeclampsia outcomes Despite numerous studies and advances in identifying the pathophysiologic mechanisms, preeclampsia remains the disease of theories involving endothelial dysfunction, 20 metabolic abnormalities 21 and inammatory activa- tion; 22,23 each of these entities may reect genetic predis- posing factors. 24,25 However, the search for biological markers to predict preeclampsia remains ongoing. 2631 Recent epidemiological studies indicate that pre- eclampsia is not just a pregnancy-related disease that resolves with delivery. In fact, preeclampsia may be considered a risk marker for later-life diseases, including cardiovascular and renal diseases, as most recently sug- gested. 32 Whether preeclampsia directly contributes to these diseases or simply unmasks preexisting shared risk factors is unknown. The two-stage model of defective placentation and impaired spiral artery remodeling fol- lowed by maternal systemic manifestations may now be considered to include a third, later-life stage of long-term chronic endothelial and metabolic dysfunction. Studies that have investigated the etiology and pre- vention of eclampsia have also provided evidence that seizures may be the result of an underlying hypertensive encephalopathy. 33 First described in 1996, hypertensive encephalopathy associated with specic neuroradiologic imaging has been named posterior reversible encepha- lopathy syndrome (PRES). 34 PRES is characterized by headaches, seizures, altered mental status, and visual disturbances and has been found in patients with pre- eclampsia, renal failure, and hypercalcemia and those taking immunosuppressive and chemotherapeutic drugs. The purported mechanism of PRES includes endothelial dysfunction, acute increases in blood pressure that may exceed the upper limit of cerebral autoregulation, and vasogenic edema. A number of publications have reported PRES in the peripartum period, some of which, 35,36 but not all, 3740 noting an association with preeclampsia. Two cases of PRES have occurred in the presence of postdural puncture headache, which compli- cates the recognition and management of the dis- ease. 36,40 The prompt diagnosis of PRES is critical for early management of hypertensive encephalopathy and to prevent subsequent irreversible white matter lesions of the brain. Dyer et al. 41 emphasized the important role that anesthesiologists play in the management of these sick women, particularly in regards to regulating the hemodynamic and cardiovascular effects of neuraxial anesthesia during cesarean delivery. To test the hypothesis that the hypertensive encepha- lopathy underlying eclampsia causes white matter dam- age that might impair long-term cognitive function, Aukes et al. 42 evaluated 30 women formerly diagnosed with eclampsia, 31 women with preeclampsia, and 30 healthy parous controls. The Cognitive Failures Ques- tionnaire was used to assess the likelihood of commit- ting errors during the completion of daily tasks; women who had experienced eclamptic seizures were shown to have decient cognitive function including memory impairment and distractibility. The study indi- cated the potential importance of preventing eclamptic seizures and suggested that full clinical recovery after eclampsia may not be expected. Finally, a systematic review and meta-analysis of 25 trials (n = 3,488,260 women) by Bellamy et al. 43 to assess the risk for cardiovascular disease and cancer later in life, revealed that preeclampsia appears to be associated with an increased risk for hypertension, fatal and non-fatal ischemic heart disease (particularly with the onset of preeclampsia before 37 weeks of gestation), strokes and venous thromboembolism. Preeclampsia was not associated with an increased risk for cancer in this review, although lower breast cancer risks in for- merly preeclamptic women have been suggested by others. 44 Conclusions The literature published in 2007 has generated evidence highlighting pregnancy, labor and delivery as crucial events that have the potential to impact womens health and well-being long after delivery. Obstetric anesthe- siologists should seize the opportunity to: (1) provide optimal low-dose labor analgesia, (2) prevent persistent and disabling post-partum pain by identifying and treat- ing women prone to severe pain with multimodal post- cesarean delivery analgesia, and (3) control maternal 370 Whats new in obstetric anesthesia hypertension in preeclamptic women to prevent the devastating outcomes associated with hypertensive encephalopathy, posterior reversible encephalopathy syndrome, and seizures. References 1. Caton D. A century of spinals for childbirth. 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