Latest & Greatest Trends in OB Anesthesia Holly Ende, M.D. Assistant Professor Division of Obstetric Anesthesiology Vanderbilt University Medical Center

I have no disclosures

October 2017 December 2017 And as I was preparing Over past months

LABOR ANALGESIA CESAREAN ANESTHESIA HEMORRHAGE OPIOID USE

LABOR ANALGESIA

LABOR ANALGESIA Neuraxial Anesthesia Nitrous Oxide

Maternal satisfaction Need for manual anesthetic interventions Labor progression Mode of delivery For a good review of the current data 9 RCT George RB, et al. Anesth Analg 2013; 116(1):133-144

Maternal Satisfaction PIEB --- CEI 4/5 George RB, et al. Anesth Analg 2013; 116(1):133-144

Need for Manual Anesthetic Interventions Cumulative data favorable not statistical significance George RB, et al. Anesth Analg 2013; 116(1):133-144

Labor Progression George RB, et al. Anesth Analg 2013; 116(1):133-144

Mode of Delivery: Instrumented VD And finally 1/9 designed and powered Pooled results approached George RB, et al. Anesth Analg 2013; 116(1):133-144

Mode of Delivery: CD George RB, et al. Anesth Analg 2013; 116(1):133-144

 Maternal satisfaction  Instrumented vaginal delivery rate (?)  Need for anesthesia intervention (?) George RB, et al. Anesth Analg 2013; 116(1):133-144

TREND: PIEB likely has benefits over CEI and is gaining popularity in obstetric units throughout the country ideal regimen dose, interval, drug concentration

LABOR ANALGESIA Neuraxial Anesthesia Nitrous Oxide

Is it effective? Are patients satisfied? Blender devise (Nitronox) or premixed (Entonox) Likis FE et al. Anesth Analg 2014; 118(1):153-67

Proportion of “very effective” responses Effectiveness Retrospective questionnaire study (n=2482) 2 months postpartum Proportion of “very effective” responses Primiparas Multiparas Epidural 84% 72% Nitrous 38% 49% Waldenstom U et al. J Psychosom Obstet Gynaecol 2006; 27(3):147-56

Satisfaction Retrospective survey study (1999, Sweden) Nitrous oxide associated with dissatisfaction with birth experience (independent of pain scores) Prospective RCT (2000, Kuala Lumpur) Nitrous oxide group less satisfied with pain relief compared to epidural group (p<0.01) Waldenstrom U, et al. J Psychosom Res 1999; 47:471-82 Leong EW, et al. J Obstet Gynaecol Res 2000; 26:271-5

Vaginal deliveries with anesthetic care N=6242 Nitrous oxide Delivered with nitrous N=753 (60%) Converted to neuraxial N=493 (40%) Neuraxial anesthesia N=5261 (81%) Richardson MG. Anesth Analg 2017; 124(2):548-53

Effectiveness Satisfaction Richardson MG. Anesth Analg 2017; 124(2):548-53

TREND: Nitrous oxide is gaining popularity in the U. S TREND: Nitrous oxide is gaining popularity in the U.S. as a labor analgesic and appears safe and reasonably effective in certain populations

CESAREAN ANESTHESIA

CESAREAN ANESTHESIA Norepinephrine

Norepinephrine during Cesarean Delivery Phenylephrine Reflex bradycardia ( agonist)  Cardiac output Norepinephrine  Negative effects on (+ agonist) HR and CO While norepinephrine is certainly not a common choice

Computer-controlled infusion Starting dose: Norepinephrine 2.5 µg/min Phenylephrine 50 µg/min CO 5min after induction greater in NE group One investigator in particular 104 computer-controlled closed-loop primary outcome greater HR (decreased incidence bradycardia), lower SVR, similar neonatal outcomes suprasternal Doppler (USCOM 1A Cardiac Output Monitor) Ngan Kee WD, et al. Anesthesiology 2015; 122(4):736-45

Intermittent NE bolus (3, 4, 5, 6, 7, or 8 µg) when SBP<100% baseline Primary outcome: success to maintain SBP≥80% from induction to delivery ED90 ~ 6 µg Onwochei DN, et al. Anesth Analg 2017; 125(1):212-18

Norepinephrine Protocol Group 1 (infusion) Started 2.5 ug/min Titrated 0-5 ug/min Group 2 (bolus) No ppx vasopressor 5 ug bolus when SBP<80% baseline 110 primary outcome was the incidence of hypotension from IT injection through delivery, incidence and timing – using survival analysis systolic blood pressure was maintained closer to baseline in the infusion group Ngan Kee WD, et al. Anesth Analg 2017; Epub ahead of print

Norepinephrine Protocol ≥ 1 Hypotensive Episode(%) Total norepinephrine (median [IQR]) Group 1 (infusion) Started 2.5 ug/min Titrated 0-5 ug/min 17% 61.0 µg [47.0-72.5] Group 2 (bolus) No ppx vasopressor, 5 ug bolus when SBP<80% baseline 66% 5.0 µg [0-18.1] The infusion group also had significantly fewer episodes of hypotension overall as well as increased total dose of norepinephrine administered Ngan Kee WD, et al. Anesth Analg 2017; Epub ahead of print

TREND: Dilute solutions of norepinephrine may be a reasonable alternative to phenylephrine for treatment of post-spinal hypotension

HEMORRHAGE

HEMORRHAGE TXA Oxytocin

WOMAN TRIAL WOMAN Trial Collaborators. Lancet 2017; 389:2105-16 2010 and 2016 20,000 death due to bleeding (shown in this forest plot) within 3 hours of birth flaws in study design primary outcomes were adjusted mid-trial WOMAN Trial Collaborators. Lancet 2017; 389:2105-16

“Given the mortality reduction findings, tranexamic acid should be considered in the setting of obstetric hemorrhage when initial medical therapy fails.” Obstet Gynecol 2017; 130(4):923-5

WOMAN TRIAL: Trial Sites Nigeria Pakistan Uganda Kenya Cameroon Sudan Tanzania Nepal Zambia Albania Democratic Republic of Congo Bangladesh Ethiopia Burkina Faso Ghana clinical practice very different (early hyst, no blood, higher mortality rate) Overall mortality rate 2.3-2.6% Mortality 2/2 bleeding 1.5% (TXA) vs. 1.9% placebo WOMAN Trial Collaborators. Lancet 2017; 389:2105-16

WOMAN TRIAL: Complications safe (no thrombotic side effects) mechanism makes sense (fibrinolysis is major component of PPH) No difference in thromboembolic events or other complications (renal failure, cardiac failure, resp failure, hepatic failure, sepsis, seizure) WOMAN Trial Collaborators. Lancet 2017; 389:2105-16

TREND: There is now data to suggest that TXA may be beneficial in the setting of uncontrolled PPH

HEMORRHAGE TXA Oxytocin

Oxytocin: NONLABORING Women Reference Year Study Design Oxytocin Dosing Outcome Carvalho et al. 2004 Biased coin up-down method 0.5 IU starting dose ED90 = 0.35 IU George et al. 2010 0.4 IU/min starting dose ED90 = 0.29 IU/min Sarna et al. 1997 RCT 5, 10, 15, 20 IU bolus No difference in uterine tone between groups Butwick et al. 0, 0.5, 1, 3, 5 IU bolus Balki M, et al. Anesthesiol Clin 2014; 52:48-66

Oxytocin: LABORING Women Reference Year Study Design Oxytocin Dosing Outcome Balki et al. 2006 Biased coin up-down method 0.5 IU starting dose ED90 = 2.99 IU Munn et al. 2001 RCT 10 IU/500 ml over 30 min 80 IU/500 ml over 30 min 39% additional uterotonics 19% additional uterotonics Balki M, et al. Anesthesiol Clin 2014; 52:48-66

Level A Recommendations All obstetric care facilities should have guidelines for the routine administration of uterotonics in the immediate postpartum period Uterotonic agents should be the first-line treatment for postpartum hemorrhage caused by uterine atony The specific agent selected is at the health care provider’s discretion Level B Recommendations When uterotonics fail to adequately control postpartum hemorrhage, prompt escalation to other interventions are indicated Tranexamic acid should be considered when initial medical therapy fails Recommend existence of a designated multidisciplinary response team, a staged postpartum hemorrhage protocol that includes guidelines for escalation of care, and a functioning massive transfusion protocol No specific mention of oxytocin for prophylaxis or treatment of hemorrhage, nor any recommended dosing regimens Obstet Gynecol 2017; 130(4):923-5

WHO Guidelines for the Management of PPH Dose and route IV: Infuse 20 units in 1L IV fluids at 60 drops/min Continuing dose IV: Infuse 20 units in 1L IV fluids at 40 drops/min Maximum dose Not more than 3L of IV fluids containing oxytocin Precautions/ Contraindications Do not give as an IV bolus No differentiation between laboring/nonlaboring WHO guidelines; 2009

Balki M, et al. Anesthesiol Clin 2014; 52:48-66

TREND: Oxytocin doses can be lowered to minimize side effects while still achieving adequate uterine tone

OPIOID USE

The Ideal Opioid Prescription Meet patients’ analgesic requirements Minimize leftover opioids severity and duration of pain Normative opioid utilization patterns

2 week postpartum telephone interview 85% filled opioid prescription at discharge 84% with unused tablets survey study across 6 academic institutions in the US contacted by phone 2 weeks following cesarean delivery pain control and opioid use 720 subjects were included in the analysis Bateman BT, et al. Obstet Gynecol 2017; 130:29-35

Patterns of Opioid Prescription and Use After Cesarean Delivery Tablets dispensed predicts Median # prescribed: 40 Median # consumed: 20 The largest predictor of the number of tablets consumed by subjects was the number of tablets they had been prescribed, EVEN AFTER adjusting for confounders such as pain scores Tablets consumed Bateman BT, et al. Obstet Gynecol 2017; 130:29-35

Patterns of Opioid Prescription and Use After Cesarean Delivery >opioid related side effects > tablets consumed when more were dispensed NO DIFF pain scores at 1 or 2 weeks satisfaction with pain control need for refills Bateman BT, et al. Obstet Gynecol 2017; 130:29-35

TREND: Tailored opioid prescriptions post-cesarean delivery may help to prevent overprescribing and potential for diversion shared decision making algorithm-based prescribing based on inpatient opioid consumption

Benefits of PIEB include improved maternal satisfaction and likely need for fewer “top ups” Nitrous oxide is associated with reasonable effectiveness and satisfaction in motivated patients Norepinephrine may be a reasonable alternative to phenylephrine for treatment of post-spinal hypotension

TXA should be considered in the setting of uncontrolled PPH Oxytocin doses can be lowered to minimize side effects while still achieving adequate uterine tone Tailored opioid prescriptions post-cesarean delivery may help to prevent overprescribing and potential for diversion