Nonobstetric Surgery during Pregnancy Are we ready Berrin

Nonobstetric Surgery during Pregnancy: Are we ready? Berrin Günaydin, MD, Ph. D Gazi University Faculty of Medicine Department of Anesthesiology, Ankara, Turkey 1

Multidisciplinary approach is a must for non-obstetric surgery during pregnancy

Epidemiology Each year over 75000 ( 87000) pregnant women in USA undergo nonobstetric surgery Semin Perinatol 2002 Chestnut’s 2009 Each year 5700 -76000 ( 115000) pregnant women in EU undergo nonobstetric surgery Minerva Anestesiol 2007 Chestnut’s 2009

Epidemiology Need for nonobstetric surgery 0. 75%-2% (0. 3%-2. 2%) J Clin Anesth 2006 Chestnut’s 2009 42% during the 1 st trimester 35% during the 2 nd trimester 23% during the 3 rd trimester These operations are either directly (such as; cerclage) or indirectly (such as; appendectomy) related to pregnancy Semin Perinatol 2002

FETAL CONCERNS Risk of Teratogenicitiy § Organogenesis is between 15 -70 days after last menstrual period Manifestations of teratogenicity § Death (abortion, fetal death and stillbirth in humans and fetal resorption in animals) § Structural abnormalities § Growth restriction § Functional deficiencies are usually associated with exposure during late pregnancy or after birth (4 th intrauterine month to 2 nd postnatal month) IARS 2006

Risk of Teratogenicity During maintaining normal maternal physiology § local anesthetics § volatile anesthetics § induction agents (barbiturates, ketamine and propofol) § muscle relaxants (wide margin of safety because of limited placental transfer) § opioids are not teratogen in clinical concentrations §Evidence does not support association between diazepam & craniofacial defects §N 2 O is a weak teratogen in rodents by inhibiting methionine synthase which alters DNA synthesis under certain conditions (at 50% concentrations for 24 hours) §No human data support increased risk for congenital anomalies Minerva Anestesiol 2007 IARS 2006 J Clin Anesth 2006

FETAL CONCERNS Preterm Labor § It is unclear whether nonobstetric surgery, manipulation of uterus or underlying condition is responsible from increased incidence of preterm delivery and abortion § 22% of 778 patients who underwent appendectomy between 24 to 36 weeks gestation delivered within first week after surgery Mazze &Kallen. A Swedish registry study of 778 cases. Obstet Gynecol 1991 § No increased risk of delivery one week after surgery § 2 nd trimester procedures and those not involving uterine manipulation carry the lowest risk of preterm labor

FETAL CONCERNS Preterm Labor § Evidence doesn’t suggest that any anesthetic agent or technique influence the risk of preterm labor § Prophylactic tocolytics may be considered but are associated with side effects (it is unclear whether they affect the outcome due to their limited efficacy for prevention of preterm labor) § Selective administration at high risk patients (e. g. cervical cerclage) or after 24 weeks gestation § Additional surveillance is required for patients receiving potent analgesics postoperatively

FETAL CONCERNS Nondrug Factors § Prolonged hypoxia and hypercarbia and severe hypoglycemia § Maternal stress and anxiety § Hyperthermia (teratogen in humans and animals) § congenital CNS anomalies associated with maternal fever >38. 90 C during 1 st half of pregnancy § Ionizing radiations (teratogen in humans and animals) § No increase in anomalies/growth restriction from exposure <5 -10 rads

Behavioral Teratology § Anesthetics act by potentiation of GABAA receptors or antagonism of NMDA receptors induce widespread neuronal apoptosis during period of synaptogenesis § Result in hippocampal (cornu ammonis: CA & dentat gyrus: DG) synaptic function deficit and persistent memory/learning impairments § The implications for human fetus or infants is unknown Jevtovic-Todorvic et al. Early exposure to common anesthetic agents causes widespread neurodegeneration in developing rat brain and persistent learning deficits. J Neurosci 2003

Role of ketamine on the apoptotic effect of isoflurane in rats Kartal S, Gunaydin B. • Effects of ketamine (NMDA receptor antagonist) on the isoflurane (GABA-A agonist) induced apoptotic neurodegeneration was investigated • Apoptotic neurodegeneration has been shown in hypocampus (CA-1 and dentat gyrus) which was mediated by caspase 3, 8 and 9 • Significantly more immunoreactive cells for caspase 3, 8 and 9 in group Iso+Ket were observed in the hypocampus • Isoflurane induced apoptosis in rats increased by ketamine

Caspase 8 Caspase 9 CA-1 Caspase 3 DG

Uteroplasental Perfusion & Fetal Oxygenation Causes of hypoxia § § § Difficult intubation Esophageal intubation Pulmonary aspiration High levels of regional block Systemic local anesthetic toxicity Airway compromise from trauma § § § § § Causes of decreased uteroplacental perfusion Aortocaval compression High spinal or epidural blockade Hemorrhage Hypovolemia Hyperventilation Deep levels of general anesthesia High dose of ά adrenergic agents Increased circulating catecholamines Uterine hypertonus from ketamine >2 mg/kg in early pregnancy or toxic doses of local anesthetics

TIMING OF SURGERY § Elective surgery should not be performed during pregnancy § Surgery should be avoided during the 1 st trimester § 2 nd trimester is the optimal time § Urgent operations like abdominal emergencies, malignancies, neurosurgical and cardiac conditions § In serious maternal illness, primary goal is to preserve mother’s life § Simultaneous C/S or prior to surgical procedure to avoid fetal risks associated with special patient positioning (sitting or prone position), prolonged anesthesia, major intraoperative blood loss, maternal hyperventilation, deliberate hypotension or cardiopulmonary bypass

FETAL MONITORING § Continuous FHR monitoring (using transabdominal doppler) feasible after 18 weeks of gestation § FHR variability manifests after 25 to 27 weeks of gestation § FHR patterns from drug effects (opiates, induction and inhalation agents) should be distinguished from fetal hypoxia § FHR monitoring allows optimization of intrauterine environment § Nonreassuring pattern may indicate need to improve maternal oxygenation, increase blood pressure, increase uterine displacement, change site of surgical retraction or begin tocolysis

FETAL MONITORING According to ACOG opinion § “The decision to use intraoperative FHR monitoring should be individualized and each case warrants a team approach for safety of woman and her baby” § Plan should be in place for proceeding with urgent or emergent cesarean delivery in the event of persistent nonreassuaring FHR pattern 17

Anesthetic Management Preoperative care Preanesthetic medications Preoperative medication is traditionally withheld • Sedatives are usually avoided (if necessary, 0. 5 -2 mg midazolam and/or 2550 µg fentanyl can be considered) • Glycopyrolate (Anticholinergic agent of choice) Does not readily cross the placenta Prophylaxis §H 2 receptor antagonists §Metoclopramide (10 mg IV) Cholinergic agonist peripherally Dopamin receptor antagonist centrally Increases lower esophageal sphincter tone (antiemetic effect) Reduces gastric volume by increasing gastric peristalsis Crosses placenta but no significant effect on the fetus §Clear nonparticulate antacids §Sodium bicitra ( oral 30 m. L) Kuczkowski KM. Arch Gynecol Obstet 2007 Reduces gastric acidity

Anesthetic Management §Prevention of aortocaval compression §Positioning must ensure 15⁰ left lateral tilt (since changes in maternal position can have profound hemodynamic effects, either Trendelenburg or reverse Trendelenburg’s positions should be carried out slowly) J Clin Anesth 2006 §Maternal and fetal monitoring §ECG, heart rate, Sp. O 2 and ETCO 2 §Blood pressure (noninvasive or invasive) §Peripheral nerve stimulator §Temperature §FHR and uterine activity Chestnut’s. Obstetric Anesthesia Principles and Practice 2009

Anesthetic Technique Both regional and general anesthesia techniques have been successfully used for nonobstetric surgery Regional Anesthesia § § §Decreased protein binding due to low albumin §Increased sensitivity to peripheral neural blockade §More extensive blockade with epidural and spinal anesthesia § § General Anesthesia Rapid sequence IV induction Denitrogenation (100% O 2 for 5 min) Effective cricoid pressure Endotracheal intubation is mandatory In case of failed intubation, LMA can be used in the reverse Trendelenburg’s position for brief periods Alveolar hyperventilation, reduction of FRC and 30% reduction of MAC Decreased thiopental requirements J Clin Anesth 2006

EFFECTS OF ANESTHETIC AGENTS ON THE FETUS Inhalation agents Intravenous induction agents Neuromuscular blocking agents §Decreased plasma § N 2 O may impair DNA§ Thiopental history of safe use cholinesterase levels by 25% §Prolonged neuromuscular synthesis and inhibit § (propofol added to list later) blockade with Sch is cell division § Benzodiazepines are avoided uncommon due to increased Vd § No evidence suggests during organogenesis reproductive toxicity § Narcotics may be related to with sevoflurane or intrauterine fetal asphyxia desflurane in clinical § Morphine and fentanyl have concentrations also history of safe use Chestnut’s. Obstetric Anesthesia Principles and Practice 2009 §Vecuronium when Sch is contraindicated (prolonged duration) §Rocuronium alternative to SCh in high doses (longer duration of action) §Cis-atracurium less desirable for RSI (shorter duration due to Hoffman’s elimination in vivo)

Reversal Agents § Anticholinesterases have a theoretical concern because of increased uterine tone that may precipitate preterm labor § Transplacental transfer of anticholinesterase is predicted as limited due to molecular size & structure of neostigmine but it can have significant fetal effecs § Although atropine which readily crosses placenta may cause fetal tachycardia and loss FHR variability, it may be preferable to counteract fetal effects of neostigmine instead of glycopyrolate IARS 2006

Postoperative Care § FHR and uterine activity should be monitored during recovery from anesthesia § Satisfactory maternal analgesia can be achieved with systemic narcotic PCA or PCEA when available § Regional analgesia provides better pain relief and less effect on FHR variability § Use of NSAI drugs is avoided (because of potential premature closure of DA and development of oligohydramnios) 24

Specific Situations §Laparoscopy §Cardiac surgery requiring CPB §Neurosurgery §Malignancy- metastatic breast cancer requiring surgery

Type of surgery § Laparoscopic surgery The most common abdominal procedures § Appendectomy 1/1500 -2000 pregnanccy § Cholecystectomy 1 -8/10000 pregnancy § Cardiac surgery requiring bypass § Neurosurgery J Clin Anesth 2006

SAGES Committee Opinion I. Obtain an obstetric consult preoperatively II. Delay elective cases until 2 nd trimester III. Use lower ext pneumatic compression devices (pregnancy and pneumoperitoneum may induce a hypercoagulable state) IV. Follow maternal and fetal physiologic status intraoperatively (maternal ETCO 2) Society of American Gastrointestinal Endoscopic Surgeons (SAGES) Guidelines for laparoscopic surgery during pregnancy

SAGES Committee Opinion V. Protect uterus with lead shield for intraoperative cholangiography VI. Use open technique to gain pneumoperitoneum VII. Tilt table left side down to move gravid uterus off vena cava VIII. Minimize pneumoperitoneum to 8 to 12 mm Hg Society of American Gastrointestinal Endoscopic Surgeons (SAGES) Guidelines for laparoscopic surgery during pregnancy

Appendectomy § The most common nonobstetric surgical emergency during pregnancy § Appears to occur more frequently in the 2 nd and 3 rd trimesters § The mortality of appendicitis complicating pregnancy is the mortality of delay

Laparoscopic Surgery During Pregnancy Adding pneumoperitoneum to an enlarged uterus § § § Limits diaphragm expansion Increases peak airway pressure Decreases FRC Decreases thoracic cavity compliance Increases ventilation-perfusion mismatching

Laparoscopic Surgery During Pregnancy § CO 2 pneumoperitoneum hypercapnia and hypoxemia § Hyperventilation reduce uteroplacental blood flow § Reduced venous return and cardiac index significant hypotension § Intermittent pneumatic compression devices and thrombophylaxis are important

Cardiac surgery during pregnancy © Incidence of heart disease in pregnancy 1%-4% © Decompensation may peak at 28 to 30 weeks © Maternal mortality rate 20% to 35% © Cardiac surgery indications are few © © © © Severe valve disease Malfunction of prosthetic valve Major vessel disease Traumatic aortic rupture Pulmonary embolism Heart tumor Patent foramen ovale Clin Obstet Gynecol 2009

Cardiac surgery during pregnancy § § Fetal bradycardia is common during bypass Hypothermia is associated with uterine irritability Duration of CPB does not affect fetal outcome Maternal temperature above 29. 5⁰C is associated with better fetal survival § Highest maternal mortality occurs if surgery is performed at delivery or immediately postpartum Clin Obstet Gynecol 2009

CPB © Moderate hypothermia during bypass © Persistent fetal bradycardia © Warm cardiopulmonary bypass will improve © Increase pump flow, if FHR<80 bpm © Ensure adequate uteroplacental perfusion © Maintain pump flow 30 -50% greater than usual © Maintain perfusion pressure at or above 60 mm. Hg © Avoid aortocaval compression © Optimize acid-base status, oxygenation, and ventilation Kuczkowski KM, CME Rev 2003

• • • 24 year old parturient at 32 weeks’ gestation 158 cm, 60 kg Severe mitral stenosis Open mitral commissurotomy General anesthesia – Induction with propofol, fentanyl, pancuronium – Maintenance by TIVA • Continuous FHR monitorization • CPB under mild hypothermia (30 -32ºC)

• 10 min after aortic cross clamping, progressive decelerations in FHR tracing followed by asystole • After rewarming, heart was defibrillated and CPB was discontinued • Then, protamine was administered • Since no FHR, pregnancy termination was considered by obstetricians • However, 2 hours after patient was transferred to the ICU, normal and rhythmic FHR returned • Parturient vaginally delivered at term • Authors conclude that loss of fetal heart sounds during CPB should not always indicate fetal death

Neurosurgery During Pregnancy Neurosurgical Approach § Controlled hypotension (Volatile anesthetic, nitroglycerin or nitroprusside) § Reduction in SBP of 25 -30% or MBP< 70 mm. Hg causes reduction in uteroplacental blood flow Nitroprusside § crosses placenta resulting in fetal hypotension § converted to cyanide (may cause significant toxicity & fetal death) § Discontinue if Infusion rate> 0. 5 mg/kg/hour Maternal metabolic acidosis Resistance to the agent § Hypothermia - Fetal bradycardia § Hyperventilation Decreased placental O 2 transfer & umbilical vessel vasoconstriction § Diuresis - Significant negative fluid shift for fetus

§ § § Case 2: Sequential operation (C/S followed anterior corpectomy & posterior spinal decompression) at 34 weeks’ of gestation 38 yr old parturient who underwent radical mastectomy and chemotherapy 9 years ago due to invasive ductal Ca stage II/III Admitted with paraplegia due to spine metastasis at 31 weeks 1850 g healthy baby was delivered by C/S under general anesthesia Rapid sequence IV induction with propofol and Sch (7. 0 mm cuffed tube) After delivery, anesthesia was maintained in 0. 7 MAC isoflurane and remifentanil infusion

Clinical Suggestions ü All women between 12 to 50 years should have the last menstrual period documented ü If pregnancy is diagnosed, surgery is postponed until 2 nd trimester if possible ü Elective surgery is postponed until after delivery, if not possible then 1 st trimester should be avoided ü 1 st trimester: theoretical risk of teratogenicity is increased ü 2 nd trimester: optimal time to perform surgery ü 3 rd trimester: preterm labor and maternal risk is high J Clin Anesth 2006

Objectives for anesthetic management during non-obstetric surgery • • Provide maternal safety Avoid using teratogenic drugs Maintain uteroplasental perfusion by preventing intrauterine fetal asphysia Avoid preterm labor

Potential teratogens during pregnancy • • • • • Angiotensin converting enzim inhibitors Alkol Androjenler Antitiroid drugs Carbamazepin Chemotherapeutic drugs Cocaine Coumadin Dietilstilbesterol Lead Lithium Mercury Phenytoin Radiation (>0. 5 Gy) Streptomycine/Canamycine Tetracycline Trimetadion Valproic acite Vitamine A

ACOG Committee Opinion No: 474 Nonobstetric surgery during pregnancy ACOG Committee on Obstetric Practice Obstet Gynecol. 2011 Feb; 117(2 Pt 1): 420 -1 The American College of Obstetricians and Gynecologists' Committee on Obstetric Practice acknowledges that the issue of nonobstetric surgery during pregnancy is an important concern for physicians who care for women. It is important for a physician to obtain an obstetric consultation before performing nonobstetric surgery and some invasive procedures (eg, cardiac catheterization or colonoscopy) because obstetricians are uniquely qualified to discuss aspects of maternal physiology and anatomy that may affect intraoperative maternal-fetal well-being. Ultimately, each case warrants a team approach (anesthesia and obstetric care providers, surgeons, pediatricians, and nurses) for optimal safety of the woman and the fetus

• • • • Arch Gynecol Obstet. 2007 Sep; 276(3): 201 -9. Epub 2007 Mar 13. Laparoscopic procedures during pregnancy and the risks of anesthesia: what does an obstetrician need to know? Kuczkowski KM. Source Department of Anesthesiology, University of California San Diego (UCSD) Medical Center, 200 W. Arbor Drive, San Diego, CA 92103 -8770, USA. kkuczkowski@ucsd. edu Abstract BACKGROUND: Nonobstetric surgery may be necessary during any stage of gestation. METHODS: The purpose of this article is to review the current recommendations (using Medline search for the relevant publications) for the perioperative anesthetic management of pregnant women undergoing laparoscopy for indications unrelated to pregnancy. RESULTS: The current estimates of the incidence of nonobstetric surgery in pregnancy range from 1% to 2%. Laparoscopy is the most common surgical procedure performed in the first trimester of pregnancy, whereas appendectomy is the most common procedure performed during the remainder of pregnancy. CONCLUSIONS: In the past pregnancy was considered as an absolute contraindication to laparoscopy. However, recent years have brought an extensive experience with this technique during gestation.

ACOG Committee on Obstetric Practice acknowledges that the issue of nonobstetric surgery and anesthesia in pregnancy is an important concern for physicians who care for women. However, there are no data to allow us to make specific recommendations. Number 284, August 2003

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