Anesthetic and Analgesic Methods Used for OB Anesthesia

Anesthetic and Analgesic Methods Used for OB Anesthesia New Innovations Joseph E Pellegrini, Ph. D, CRNA Associate Professor Deputy Program Director University of Maryland Nurse Anesthesia Program

Obstetrical Anesthesia o Evolution taking place n n Use of CLE from 16% in 1985 to > 50% in 2000 Practice changes o n Consumerism o n Litigation Increased demands on Anesthesia Providers o n Introduction of new drugs, techniques, and delivery apparatus 24/7 coverage Increased research in OB anesthesia arena o Promoted changes in Anesthesia Dept. guidelines

Goals of Laboring Analgesia o Principle Goal n Delivery of a healthy neonate o o Expelling the fetus & placenta Three distinct stages of Labor n Each stage has different analgesic requirements

Pain of Parturition

Pain Centers during labor progression

Initiation of Epidural Analgesia o o Continue to have controversy as to when to initiate epidural analgesia Some advocate waiting until 4 cm dilatation whereas others initiate at request n n Early initiation associated with prolonged stages of labor Early initiation associated with increased dystocia, instrumental and operative delivery rates o Recent study dispute these claims

Early Late

Outline o New Innovations for Laboring Analgesia n n CSE Technique Patient Controlled Epidural Analgesia o o o With or without a basal infusion rate With or without predetermined timed boluses New Innovations for Cesarean Section n Opioids administered for postoperative analgesia o o Depo. Dur for postoperative analgesia Side effect prophylaxis n Control of opioid induced side effects

The CSE Technique o Viewed as most significant advancement in OB anesthesia in the last decade o CSE - Usually performed using a needle-thru-needle technique n Intrathecal opioids very effective in controlling 1 st stage labor pain o n Fentanyl 10 -25 ug or Sufentanil 5 -7. 5 ug with/without morphine 0. 1 -0. 25 mg and/or bupivacaine 2. 5 mg n Addition of bupivacaine efficacy in question – typically not efficacious for 2 nd stage labor pain Need adequate amounts of local anesthetics to effectively block the pain for 2 nd stage labor pain o Routinely administered via CLE

The CSE Technique o CSE technique often given in combination with an epidural infusion n Traditional Method – o Bolus before infusion n Traditional Admixtures o o o CLE infusion (continuous infusion) o o n . 125% -. 25% Bupivacaine with/without 50 -100 mcg fentanyl. 2% Ropivacaine with/without 50 -100 mcg fentanyl 0. 1 -0. 125% Bupivacaine with or without 1 -2 mcg/ml fentanyl at 8 -15 ml/hr 0. 125 -0. 2 Ropivacaine with or without 1 -2 mcg/ml fentanyl at 8 -15 ml/hr Alternative Method o Patient Controlled Epidural Analgesia (PCEA) Becoming more popular in OB anesthesia practices Often administered immediately following placement of intrathecal opioids with small basal rates and set maximum hourly dose Advantages o Less variability in the peak plasma concentration of drug o Faster onset of analgesia o Titrate able o Greater pain control and Satisfaction scores noted when compared to traditional continuous infusion rates o n n

CSE for Cesarean Delivery o CSE use during c-section associated with higher sensory blockade n Conflicting results o o Both studies - CSE performed without injection or catheter placed into epidural space Anecdotal information – no differences noted in my own clinical practice when epidural catheter placed n Noted difference if test dose administered following IT injection o Epidural often used for placement of Morphine & 10 ug fentanyl administered via IT injection with 10 -12 mg hyperbaric bupivacaine o Possible difference is lateral orientation of spinal needle during injection as opposed to cephalad orientation

Patient Controlled Epidural Analgesia o o PCEA accords laboring women autonomy in pain relief for labor and has been shown to very effective and desirable Wide variety of dosing options Often dependent whether or not initial bolus dose administered following test dose Greater degree of maternal satisfaction reported when PCEA compared to conventional continuous infusion

Recipes for PCEA Anesthetic Solution Basal Rate (ml/hr) Bolus Dose (ml) Lockout interval (minutes) Maximum hourly dose (ml) Bupivacaine 0. 125% 4 4 20 20 Bupivacaine 0. 125% + fentanyl 2 mcg/ml (if bolus given) 5 3 7 18 6 -8 3 7 25 Bupivacaine 0. 25% 0 3 10 20 Bupivacaine 0. 1% + fentanyl 2 mcg/ml 10 5 10 26 Ropivacaine 0. 125% 6 4 10 24 Ropivacaine 0. 125% + fentanyl 2 mcg/ml 5 3 10 20 Bupivacaine 0. 125% + fentanyl 2 mcg/ml (if bolus not given)

PCEA versus Conventional therapy From Gambling DR, Mc. Morland GH, Yu P, Laszlo C. Comparison of patient-controlled epidural analgesia and conventional intermittent “top-up” injections during labor. Anesth Analg 1990: 70: 256 -61

PCEA o Traditionally PCEA is administered with or without a basal infusion rate n Some clinicians report that basal infusion rates not required o Omitting a basal infusion rate reduces analgesic consumption but conflicting results regarding effect on stage 2 labor and satisfaction n Recently conducted study analyzing effect on maternal hemodynamics, fetal and neonatal hemodynamics, length of stage 2 labor, effect on mode of delivery and maternal motor function and overall maternal analgesic satisfaction

Webster A, Lawson S, Nezat G, Pellegrini JE. Comparison of outcomes between groups of parturients administered PCEA laboring analgesia with and without a continuous basal infusion. 2009 Unpublished Data o Primary questions? n o What are the differences in relation to overall analgesic requirements and maternal, fetal and neonatal outcomes between groups of parturients administered a PCEA for laboring analgesia with or without a background basal epidural infusion Methods n n n 100 subjects enrolled CSE technique used – all parturients administered 10 mcg intrathecal fentanyl Parturients consented and randomized to receive PCEA laboring analgesia with or without a background basal infusion rate o o One group received PCEA alone using 0. 2% ropivacaine 5 ml boluses with a 15 min lockout (total of 20 ml/hr) One group received PCEA using 0. 2% ropivacaine 5 ml boluses with a 15 min lockout in combination with a background infusion of 0. 2% ropivacaine of 5 -10 ml/hr (maximal total set at 30 ml/hr)

Webster A, Lawson S, Nezat G, Pellegrini JE. Comparison of outcomes between groups of parturients administered PCEA laboring analgesia with and without a continuous basal infusion. 2009 Unpublished Data o o No differences in demographic variables No differences in VNRS scores for pain at any interval measurement n o No differences in mode of delivery n n n o Measured q 5 minutes following initiation for 30 minutes then q 1 hour thereafter until delivery SVD (72% in PCEA group; 80% in PCEA + CLE group) Instrument assisted (5% in PCEA group; 4% in PCEA + CLE group) Cesarean Section (23% in PCEA group; 16% in PCEA + CLE group) No differences in analgesic satisfaction scores n Both groups reported satisfaction or complete satisfaction with laboring analgesia

Webster A, Lawson S, Nezat G, Pellegrini JE. Comparison of outcomes between groups of parturients administered PCEA laboring analgesia with and without a continuous basal infusion. 2009 Unpublished Data

Webster A, Lawson S, Nezat G, Pellegrini JE. Comparison of outcomes between groups of parturients administered PCEA laboring analgesia with and without a continuous basal infusion. 2009 Unpublished Data o Conclusions n Preliminary Data o o o No differences in level of analgesia afforded PCEA alone supports previous studies regarding analgesic consumption Noted shortened stage 2 labor in PCEA alone group but no adverse effects on mode of delivery Both are viable options but data reported is preliminary Despite findings many practitioners prefer inclusion of basal rate with PCEA n Novel approach to basal rate recently investigated o Recent investigation analyzing differences between groups of parturients that received either traditional PCEA + basal continuous infusion or PCEA with automated mandatory boluses

Oxytocin at Cesarean Section o Oxytocin is routinely administered following delivery n Oxytocin can be administered immediately after delivery of the shoulders, before or after delivery of the placenta o o If administered before delivery of placenta decreased blood loss has been observed Controversy exists concerning infusion versus bolus or combination n Infusion traditionally initiated at 200 -300 m. U/min (20 U/L @ 10 ml/min or 30 U/L @ 7. 5 ml/min) for several minutes until the uterus firmly contracted and no active bleeding noted o Effect of oxytocin dependent on number of oxytocin receptors n o Pregnancy causes a 180 fold increase in concentration of oxytocin receptors with the greatest increase occuring just before the onset of labor Administration of rapid IV bolus may cause significant hypotension & cardiovascular collapse n Some practitioners advocate administration of a single IV bolus of 2 -5 units of oxytocin at time of delivery (most often in addition to infusion) o Studies have shown that administration of a 10 unit bolus can result in complete cardiovascular collapse

Bottom Line: Be vary cautious in administration of oxytocin bolus especially when faced with parturient with low MAP & Maternal pulse – can result in complete cardiovascular collapse

Cesarean Section – Postoperative Analgesia o Spinal Anesthesia n 70% of all elective cesarean sections are performed using SAB o Approximately 90% receive intrathecal morphine for postoperative analgesia n o Epidural Anesthesia n n Routinely used when epidural analgesia is used for labor Estimated that over 90% received PF Morphine Sulfate for postoperative analgesia o Dosing regimen administered (2 -5 mg) n n o o Dose ranges from 0. 10 – 0. 30 mg o Analgesia efficacy from 14 -24 hours o Moderate to high side effect profile - some studies indicating higher profile when ITN used as compared to when epidural morphine is administered Duration of action 16 -24 hours Side effect profile moderate to high Studies using conventional PF Morphine at increased doses fail to yield longer durations of action Recently investigations have been done using extended release liposome injection morphine (Depo. Dur) n Formulated in an attempt to increase the duration of analgesic action of epidural morphine

Depo-Dur o Depo. Dur (morphine sulfate extended-release liposome injection) is a sterile suspension of multivesicular liposomes using proprietary Depo. Foam® formulation technology containing morphine sulfate, intended for epidural administration. n Depo. Foam is a drug delivery system that encapsulates the morphine sulfate and allows it to be released slowly over time for a period of approximately 48 hours o o o Traditionally Dura. Morph administered to cesarean section patients in doses ranging from 2 -5 mg Depo-Dur administered to cesarean section patients in doses ranging from 5 -15 mg n o Allows analgesia for approximately twice as long as conventional Dura. Morph Studies indicate a ceiling dose effect achieved at 10 mg Recent study analyzed effect between groups of cesarean section patients administered either 10 mg Depo. Dur or 4 mg Dura. Morph n n Enrolled 70 ASA 1 and 2 cesarean section patients to receive one of the two regimens Analyzed differences in analgesic requirements, pain scores, postop activities and side effects between the groups

Carvalho B, Roland, LM, Chu LF et al. Single-dose, extended release epidural morphine (Depo. Dur™) compared to conventional epidural morphine for postcesarean section pain. Anesth Analg 2007; 105: 176 -83.

Carvalho B, Roland, LM, Chu LF et al. Single-dose, extended release epidural morphine (Depo. Dur™) compared to conventional epidural morphine for postcesarean section pain. Anesth Analg 2007; 105: 176 -83. (At rest) (With Activity)

Carvalho B, Roland, LM, Chu LF et al. Single-dose, extended release epidural morphine (Depo. Dur™) compared to conventional epidural morphine for postcesarean section pain. Anesth Analg 2007; 105: 176 -83.

Carvalho B, Roland, LM, Chu LF et al. Single-dose, extended release epidural morphine (Depo. Dur™) compared to conventional epidural morphine for postcesarean section pain. Anesth Analg 2007; 105: 176 -83. o Depo. Dur provided longer latency of analgesia and greater satisfaction n o Better analgesia 24 -48 (but was it clinically significant? ) Both conventional and Extended released morphine solution resulted in moderate to high side effect profiles n Side effects reported in the range of 20 -60% for PONV & 40 -100% for pruritis o o Side effects traditionally treated with oral histamine blockers (questionable efficacy), antiemetics or opioid antagonists (often at the expense of analgesia) There has been no definitive treatment regimen for treatment of side effects identified to use in post-cesarean section population What can we give to treat or prevent side effects in the parturient population that has been given neuraxial morphine sulfate? n Recent study analyzed effect of prophylactic IM promethazine in groups of c-section patients administered intrathecal morphine for SAB

Promethazine o Common antiemetic agent used in OB n o Two studies noted that when Promethazine administered as antiemetic agent to groups of patients administered epidural/intrathecal morphine noted a significant reduction in PONV and pruritis n n n o Possesses strong anticholinergic and antihistamine properties Both studies used small sample sizes (<20 patients) Not used in OB population Study design not specific to measure pruritis Study performed to determine if promethazine effective in preventing PONV & pruritis in a cesarean section population administered intrathecal morphine

Litchfield, J, Pronk C, Nezat G, Pellegrini JE. Effect of 25 mg IM promethazine on the incidence and severity of PONV and pruritis in a cesarean section population receiving intrathecal morphine. Accepted AANA J 2008 o o o Enrolled 60 ASA 1 & 2 subjects scheduled for elective cesarean section All subjects administered SAB with 12 mg bupivacaine, 10 mcg fentanyl and 0. 3 mg Dura Morph Randomized to receive either 25 mg IM promethazine or placebo in vastus lateralis immediately after SAB placed n n n Double blind Placebo Controlled Informed consent

Demographic Variables Promethazine Placebo Gravida (range) 1 -7 Parity (range) 0 -3 0 -4 Ethnicity Caucasian (N) African-American (N) Hispanic (N) Asian (N) 18 8 4 0 19 6 3 2 Height (Mean inches ± SD) 64 ± 2. 4 64 ± 2. 0 Weight (Mean Kg ± SD) 89 ± 17 85 ± 14 Total Surgical Time (Mean min ± SD) 47 ± 18 45 ± 17 Total PACU Stay (Mean min ± SD) 125 ± 42 125 ± 57 Litchfield J, Pronk C, Nezat G, Pellegrini JE. Effect of 25 mg IM promethazine on the incidence and severity of PONV and pruritis in a cesarean section population receiving intrathecal morphine. Accepted AANA J. 2008.

Promethazine Prophylaxis Study Findings o No difference in level of pain on injection noted between groups n o Higher incidence in level of sedation noted in placebo group n o No complaints of pain on injection reported Not Significant Apgar Scores n One Minute o o n Promethazine group range (7 -9) Placebo group range (6 -9) Five Minute o o Promethazine group range (8 -9) Placebo group range (7 -9)

Litchfield, J, Pronk C, Nezat G, Pellegrini JE. Effect of 25 mg IM promethazine on the incidence and severity of PONV and pruritis in a cesarean section population receiving intrathecal morphine. Accepted AANA J 2009

Nausea Control Satisfaction Litchfield J, Pronk C, Nezat G, Pellegrini JE. Effect of 25 mg IM promethazine on the incidence and severity of PONV and pruritis in a cesarean section population receiving intrathecal morphine. Accepted AANA J. 2009.

Pruritis Control Satisfaction Litchfield J, Pronk C, Nezat G, Pellegrini JE. Effect of 25 mg IM promethazine on the incidence and severity of PONV and pruritis in a cesarean section population receiving intrathecal morphine. Accepted AANA J. 2009.

Conclusions o o CSE is suggested method for analgesia in many OB anesthesia practices PCEA reduces analgesic requirements and increases satisfaction in some studies n o o o Basal infusion rates increase length of stage 2 labor but no adverse effects noted in relation to mode of delivery PCEA with bolus can lead to higher incidence of cesarean section Rapid infusion of oxytocin can result in significant hemodynamic instability Extended release morphine shown to be safe and effective to use in cesarean section population n Prolonged duration of analgesia o o o Some concerns over prolonged side effect profile Cannot use epidural catheter concomitantly with local anesthetic Promethazine is viable option to prevent IT and epidural opioid induced side effects in a cesarean section population

Questions? Pellegrini@son. umaryland. edu