What to Expect When Youre Not Expecting A Pregnant Patient Dr. - - PowerPoint PPT Presentation

What to Expect When You’re Not Expecting A Pregnant Patient

• Dr. Vanessa Paquette, BSc(Pharm), ACPR, PharmD

Clinical Pharmacy Specialist – Maternal Fetal Medicine Children’s and Women’s Health Center of BC

Presenter Disclosure

I have no current or past relationships with commercial entities I have received a speaker’s fee from CSHP for this learning activity

Commercial Support Disclosure

This learning activity has received no financial or in-kind support from any commercial or other

• rganization

https://stock.adobe.com/ca/images/boy-with-surprised-or-shocked-expression/7685451

Learning Objectives

• By the end of this presentation, the participant will be able to:

– Describe the physiological changes that occur during pregnancy – Interpret laboratory values in pregnant patients – Describe the utility of sepsis prognostic scores in pregnancy – Describe the pharmacokinetic changes that occur during pregnancy – Apply the pharmacokinetic changes in pregnancy to drug dosing – Treat a pregnant patient with influenza

Maternal Health

Maternal death rates rose in Canada, US over 20 years. Thomas Reuters, 2014 May 6. Available from: https://www.cbc.ca/news/health/maternal-death-rates-rose-in-canada-u-s-over-20-years-1.2633940

Public Health Agency of Canada. Perinatal Health Indicators for Canada 2013: a Report of the Canadian Perinatal Surveillance

• System. Ottawa, 2013.

Public Health Agency of Canada. Perinatal Health Indicators for Canada 2013: a Report of the Canadian Perinatal Surveillance

• System. Ottawa, 2013

Public Health Agency of Canada. Perinatal Health Indicators for Canada 2013: a Report

• f the Canadian Perinatal Surveillance System. Ottawa, 2013

Maternal Health

• Maternal morbidity and mortality is preventable
• Canada is working towards a national surveillance

system to reduce maternal morbidity and mortality

• Non-obstetric causes of death are emerging in

Canada and across the developed world as significant contributors

• Pharmacists are an essential health care provider in

the goal to improve maternal health

J Obstet Gynaecol Can 2017;39(11):1028–1037

Pharmacist Involvement in Maternal Health

• Epilepsy management and drug therapy monitoring
• Acute psychosis and chronic mental health conditions
• Treatment of substance use disorders
• Management of hypertensive disorders (pre existing and

pregnancy related)

• Asthma management
• Hyperemesis gravidarum
• Diabetes management (pre existing and gestational diabetes)

Ann Pharmacother 2012; 46: 297-300 J Pharm Technol 2016; 32(5): 191-195

Pharmacist Involvement in Maternal Health

• Pharmacokinetic-based dosing of digoxin for fetal arrhythmias
• Anticoagulant dosing and monitoring
• Treatment of acute infections including STIs
• Treatment of HIV-positive mothers and their infants
• Nutritional management (folic acid requirements, anemia)
• Preventative health including immunizations and smoking

cessation

• Contraception counseling
• Drug information in pregnancy and lactation

Ann Pharmacother 2012; 46: 297-300 J Pharm Technol 2016; 32(5): 191-195

Quiz Question: Obstetric Terminology

• G4 T1 P3 A1 L4 (PPD 4 SVD 39+2)

A) 4 pregnancies, 1 singleton at > 37 weeks gestational age (wga), 3 singletons < 37 wga, 1 abortion, 4 living children B) 4 pregnancies, 1 singleton at > 35 wga, 3 singletons < 35 wga, 1 abortion, 4 living children C) 4 pregnancies, 1 set of twins at > 37 wga, 3 singletons < 37 wga, 1 abortion, 4 living children D) 4 pregnancies, 1 singleton at > 37 wga, 1 singleton < 37 wga, 1 set of twins < 37 wga, 1 abortion, 4 living children

Case

27 year old female, G2A1, 24 wga Admitted to CTU for sepsis, source ?pneumonia

HPI

• Onset of fever, chills, sore throat, nasal congestion, body ache x 2 days,

new onset productive cough and SOB x 1 days  ER

• Febrile, tachycardic, tachypnic, SOB, 02 sat 96%, 2L NP
• Fluid, NP swab, sputum culture, pip/tazo + vanco, OB consult, fetal

monitoring, OB U/S

• Chest X ray ordered but sent back from radiology with the comment

“need to explain risks in pregnancy before imaging can be done”

PMH

• NKDA
• MRSA pneumonia 3 years ago, MRSA colonized
• Hx opioid use disorder (smoked heroin, no IVDU), last use 1 year ago,

stable on buprenorphine/naloxone 24 mg SL daily

• Major depressive disorder, stable on escitalopram 20 mg po daily
• Smokes ½ pack per day
• Therapeutic abortion (TA) 2 years ago
• Takes a prenatal vitamin daily
• Has not received the flu vaccine (pharmacy did not have a thimerisol

free product so it was recommended she not get it)

Case

Social Unemployed, lives in low income housing on the downtown eastside with her partner, pregnancy unplanned but wanted, good prenatal care Review of systems Temp 38.8, HR 110, BP 98/69, RR 20, 02 sat 96% RA CNS: A/O x 3, chills, feels tired and unwell Resp: cough, yellow-green sputum, feels SOB, crackles bilaterally, right worse than left, upper lobes clear Cardio: no chest pain, no murmurs GI: mildly nauseated GU: no cramping, no PV bleeding, normal u/o Ext: no peripheral edema Imaging ?CXR OB U/S normal growth, normal amniotic fluid volume Micro Blood cultures pending Urine culture negative Sputum culture 4+ WBC, 3+ GPC Influenza B +ve

Case

Labs Lactate 1.5 (ER 2.2 ) CBC WBC 19.3 (ER 12.6), Hgb 98, Neutrophils 16.5 (ER 9.2) Lytes Within normal limits (WNL) Liver WNL Renal Scr 70 (ER 85) TDM Vancomycin level ordered for pre 4th dose Current medication Piperacillin/tazobactam 3.375 g IV Q6h Vancomycin 1 g IV q12h Buprenorphine/naloxone 24 mg SL daily Escitalopram 20 mg po daily Dalteparin 5000 sc daily Prenatal vitamin 1 tab po daily Acetaminophen 325 – 650 mg po q4-6 h PRN

Issue #1

• There are significant physiology changes during

pregnancy, so how does that impact my assessment and monitoring of my patient’s condition? Sepsis as an example

https://stock.adobe.com/ca/images/question-mark-pregnant-belly-pregnancy-woman-problem-thinking/102770035

Sepsis in Pregnancy

• Third leading cause of maternal death worldwide (increasing in incidence in

developed countries)

• Accounts for 5% off all maternal death in developed countries
• Substandard care often identified as a contributor to mortality, usually

related to lack of recognition of sepsis

• The signs and symptoms of sepsis in pregnant women may be less distinctive

than in the non-pregnant population and are not necessarily present in all cases

• Disease progression may be much more rapid than in the non-pregnant state
• Literature and guidelines on the definition/diagnosis and management of

sepsis do not included pregnant patients (screening and monitoring/prognostic tools not validated in pregnant population)

Int J Obstet Anesth 2018; https://doi.org/10.1016/j.ijoa.2018.04.010 Reproductive Health 2017; 14:67 DOI 10.1186/s12978-017-0321-6

Green Top Guideline No. 64a. London: RCOG; 2012.

Defining Sepsis In Pregnancy

Global maternal and neonatal sepsis initiative. World Health Organization. Maternal sepsis [infographic]. Available from;: URL: http://srhr.org/sepsis/wp- content/uploads/2017/08/WHO_Infographic-Maternal-sepsis-overview-EN-A4-WEB.pdf

Int J Obstet Anesth 2018; https://doi.org/10.1016/j.ijoa.2018.04.010 Reproductive Health 2017; 14:67 DOI 10.1186/s12978-017-0321-6

Physiological Changes in Pregnancy

Changes in almost every organ system!

CV

↑ cardiac output ↑ heart rate ↓ peripheral vascular resistance ↓ arterial pressure

Heme

↑ plasma volume ↑ red cell volume ↑ white blood cells anemia

Resp

↑ tidal volume ↑ minute-ventilation ↓ residual volume ↓ PaCO2, physiologic dyspnea

Renal

↑ renal plasma flow ↑ glomerular filtration rate ureteropelvic dilation ↑ total body water

Breathe 2015: 11: 297-301. Cardiovasc J Afr 2016; 27: 89 -94 Front Pharmacol. 2014; 5: 65.

Physiological Changes in Pregnancy

GI delayed gastric emptying prolonged small bowel transit time diaphragm elevation Coag ↑ factors VII, VIII, IX, X, XII, Von Willebrand and fibrinogen ↓ protein S ↓ fibrinolytic activity BP Decreased by 5 – 10 mmHg (returns to pre pregnancy values closer to term) HR Increased by 10 – 20 bpm (approaches 90 – 100 bpm at rest during third trimester) RR Can be increased Temp No change 02 sat Target > 96%

Breathe 2015: 11: 297-301. Cardiovasc J Afr 2016; 27: 89 -94 Front Pharmacol. 2014; 5: 65.

Laboratory Values in Pregnancy

• Reported lab values will NOT reflect reference ranges for pregnant women!

BJOG 2008;115: 874–881. Obstet Gynecol 2009; 114: 1326 - 31

HgB 105 – 140 g/L (anemia < 105 – 110 g/L) WBC 6 – 16 109/L Scr Decrease 30% (20 – 30 umol/L) 30 – 70/80/90 umol/L Albumin Decrease 15 – 20% (change from 33 – 43 g/L to 23 – 33 g/L over course

• f pregnancy)

D dimer Mean > 1 mg/L by third trimester (> 2000 ug FEU/L) Alk Phos Increases by 100% (can increase to well over 200 U/L in third trimester) TSH 0.1 – 4 mU/L pH 7.4 – 7.45 PO2 PCO2 100 – 104 mmHg 27 – 32 mmHg Serum bicarb 18-22 mEq/L

Sepsis Calculators in Pregnancy

• SIRS (temp > 38 or < 36, HR > 90, RR > 20 or PaC02 <

32, WBC > 12 or < 4) – Pregnancy will not affect temperature – Pregnancy may affect HR – Pregnancy may affect RR and PaCO2 – Pregnancy may affect WBC

Obstetric patients may meet criteria for SIRS simply as a result of normal maternal physiology

Obstet Gynecol 2014;124:535–41

Am J Obstet Gynecol 2010;203:573.e1-5.

Sepsis Calculators in Pregnancy

• qSOFA (GCS > 15, RR > 22, SBP < 100)

– Pregnancy will not affect mentation – Pregnancy may affect RR – Pregnancy may affect SBP

Aust N Z J Obstet Gynaecol 2017; 57: 540–551

Sepsis Calculators In Pregnancy

• Sepsis in Obstetrics Score (SOS)

Obstet Gynecol 2017; 130: 747 - 755

Obstet Gynecol 2017; 130: 747 - 755

Obstet Gynecol 2017; 130: 747 - 755

Early Warning Scores In Pregnancy

• Modified Early Obstetric Warning System (MEOWS)

J Obstet Gynecol Can 2017; 39(9): 728-733

J Obstet Gynecol Can 2017; 39(9): 728-733

Management Of Sepsis In Pregnancy

Int J Obstet Anesth 2018; https://doi.org/10.1016/j.ijoa.2018.04.010

Issue #2

• There are significant pharmacokinetic changes during

pregnancy, so how does that impact medication dosing and monitoring? Antibiotics as an example

https://stock.adobe.com/ca/images/little-baby-with-black-board-and-red-question/192403020

Pharmacokinetic Changes In Pregnancy

PLoS Med 2016; 13(11): e1002160

Case

Current medication Piperacillin/tazobactam 3.375 g IV Q6h Vancomycin 1 g IV q12h Buprenorphine/naloxone 24 mg SL daily Escitalopram 20 mg po daily Dalteparin 5000 sc daily Prenatal vitamin 1 tab po daily Acetaminophen 325 – 650 mg po q4-6 h PRN

Vancomycin trough level = < 3 mg/L

Labs Lactate 1.5 (ER 2.2 ) CBC WBC 19.3 (ER 12.6), Hgb 98, Neutrophils 16.5 (ER 9.2) Lytes Within normal limits (WNL) Liver WNL Renal Scr 70 (ER 85) TDM

Considerations On The Use Of Vancomycin In Pregnancy:

• Pregnancy is associated with accelerated renal clearance of vancomycin and higher

volumes of distribution – Pharmacokinetic changes become more pronounced in the later stages of pregnancy and gradually return to pre-pregnancy values a few days following delivery

• Weight based dosing (avoid standard regimens)

– Use actual body weight

• Dose and target trough levels same as other adults
• May require higher dosage and shorter dosing intervals to achieve target levels

compared to non-pregnant individuals

• Recommend routine trough levels in pregnant patients

– Prior to third dose (shorter half life)

• If target levels difficult to achieve, consider drawing two levels (trough and peak) to

enable individualized pharmacokinetic calculations

Am J Health-Syst Pharm 2009;66:82-98. Clin Ther 2016; 38(9): 2006-2015

Gentamicin In Pregnancy

• Half life can be as short as 1.5 h
• Larger doses often required to reach therapeutic peak levels
• Most data in pregnancy for traditional dosing
• Once daily dosing (5 mg/kg) studied in intrapartum/postpartum

infections (chorioamnionitis, endometritis)

• Use actual body weight
• Target levels are the same

Clin Obstet Gynecol. 2008 September ; 51(3): 498–506 Obstet Gynecol 1980 Nov; 56(5):559-64.

Gentamicin In Pregnancy

What About Other Antibiotics?

PLoS Med 2016; 13(11): e1002160

What About Other Antibiotics?

• Use published adult doing guidelines
• Larger end of dosing range
• Shorter end of frequency range (time dependent killers)

PLoS Med 2016; 13(11): e1002160

Issue # 3

• We know maternal bacterial infections can have serious

complications including maternal and neonatal mortality, but should I also be thinking about influenza?

YES!

https://stock.adobe.com/ca/images/surprised-baby-girl/72553140

Influenza In Pregnancy

• Pregnant women with influenza are more likely to develop severe illness:

– Increased hospital admissions – Increased admissions to intensive care – Increased mortality

• During the 2009 H1N1 pandemic, a disproportionate number of deaths occurred among

pregnant women, who accounted for 5 percent of all deaths even though they comprised

• nly 1 percent of the United States general population
• Clinical manifestations of influenza in pregnant women are similar to those in the

general population, and include fever, cough, rhinorrhea, sore throat, headache, shortness of breath, and myalgia

• Linked to increases in fetal complications including congenital malformations (if

contracted in first trimester), spontaneous abortion, preterm delivery, small for gestational age newborn, low birth weight, and fetal demise

J Inf Dis 2012;206:1260–8 N Engl J Med 2010;362:27-35 Obstet Gynecol 2010;115:717–26

Influenza: Prevention

• Pregnant and post partum patients should receive the annual

influenza vaccine (regardless of trimester): – Any inactivated influenza vaccine (does not have to be thimerisol free) – No live vaccines

Obstet Gynecol 2018; 131(4): e109-e114

J Obstet Gynaecol Can 2018; https://doi.org/10.1016/j.jogc.2017.11.010

J Infect Dis 2016;214:507–15

Influenza: Treatment

J Infect Dis 2016;214:507–15

J Infect Dis 2016;214:507–15

Influenza Treatment

• Oseltamivir 75 mg po BID x 5 days

– Start early!

Can J Infect Dis Med 2013;24:1C – 15C

Summary

• Monitoring can be done using a modified early obstetric warning system

(MEOWS)

• When sepsis is suspected or identified, activating the sepsis resuscitation

bundle is recommended as if a non pregnant adult

• Pregnancy specific reference ranges should be used whenever possible to

interpret laboratory investigations

• Appropriate imaging should not be withheld because a woman is pregnant
• Use known physiological and PK changes in pregnancy to dose medications
• When influenza is suspected, start antiviral treatment
• Prevention is key – target pregnant women for health care prevention

measures

Questions?

http://weknowmemes.com/2013/10/disgusted-baby