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P H A R M . D . C A N D I D A T E _ _ _ _ _ _ _ _ _ _

U N I V E R S I T Y O F W Y O M I N G

S C H O O L O F P H A R M A C Y

I N T E R N A L M E D I C I N E R O T A T I O N

D A T E

Hyperemesis gravidarum Patient Case Presentation

1

Chief Complaint 2

Chief Complaint:

Intractable vomiting for ~16 hours associated with nausea and vomiting of pregnancy (NVP)

Abdominal pain secondary to vomiting

Patient Demographics

MC is a 21 year old caucasian female Height: 1.73 m (5’8’’) Actual Body Weight: 81.65 kg (180 lbs) Ideal Body Weight: 63.9 kg

Body Mass Index (BMI): 31.3 kg/m2

Estimated Glomerular Filtration Rate: 150 mL/min

3

Patient Information (Continued)

Allergies: Pineapple (Anaphylaxis) Porcine Products (Anaphylaxis)

Diphenhydramine (No description) Penicillins (No Description)

4

History of Present Illness

Patient presented at the Emergency Department 8/11 at 2000

Chief Complaint: Vomiting that commenced at 0200 on 8/11 Patient also complains of abdominal and back pain which may

be from the action of vomiting

Attempted to eat and drink and manage

Patient reported an episode of near syncope nausea and vomiting with pyridoxine, ondansetron, and doxylamine

Patient is 10 weeks pregnant

5

History of Present Illness (Continued)

Recent emergency department visits:

7/10 – Patient presented to emergency department following a fall whilst carrying a bench

7/27 – Patient presented to the emergency department with right-sided abdominal pain

8/4 – Presented to emergency department with reported hematemesis associated with nausea and vomiting of pregnancy (NVP)

6

Past Medical History (PMH) and Surgical History

PMH: Spontaneous abortion at

8 weeks Stillborn neonate at 22

weeks Asthma

Surgical History: Cholecystectomy Tonsillectomy Adenoidectomy

7

Social History (SH) and Family History (FH)

FH: No pertinent family history SH: Marital status: single Patient (Pt) reports no tobacco use Pt denies alcohol or illicit substance use Pt reports that she does attend school

8

Home Medications

Albuterol 2.5 mg/3mL nebulizer solution Signa: Take 3 mLs (2.5 mg) by nebulization every 6 hours as

needed for wheezing Indication: Asthma

Albuterol 90 mcg / actuation inhaler Signa: Inhale 2 puffs into the lungs every 6 hours as needed for

wheezing Indication: Asthma

Doxylamine-Pyridoxine 10-10 mg tablet Signa: Take 20 mg by mouth daily. Take 2 tabs at bedtime, if

symptoms persist increase to 4 tabs at bedtime for 30 days Indication: Nausea and vomiting of pregnancy

Ondansetron 4 mg orally disintegrating tablet (ODT) Signa: Take 1 tablet (4 mg) by mouth every 8 hours as needed Indication: Nausea and vomiting of pregnancy

9

Review of Systems

Constitutional: Positive for appetite change. Negative for fever and chills.

HENT: Negative for nosebleeds and rhinorrhea.

Eyes: Negative for discharge and redness.

Respiratory: Negative for choking and shortness of breath.

Cardiovascular: Negative for chest pain and palpitations.

Gastrointestinal: Positive for nausea, vomiting and abdominal pain. Negative for diarrhea.

Genitourinary: Negative for urgency and frequency.

Musculoskeletal: Positive for back pain. Negative for neck pain.

Skin: Negative for color change and rash.

Neurological: Negative for headaches.

10

Physical Exam

General appearance: awake, alert, cooperative, mild apparent distress, and appears stated age

Neurologic: grossly nonfocal HEENT: dry mucous membranes, EOMI Lungs: clear to auscultation bilaterally Heart: regular rate and rhythm, normal S1, S2 Abdomen: soft; nondistended, mildly tender to palpation diffusely Extremities: no swellings or cyanosis noted

11

Initial Vital Signs

Vital Sign Reference Range Result

Blood Pressure (mmHg) 90/60 - 120/80 105/54

Heart Rate (beats/min) 60 – 100 58

Respiratory Rate (breaths/min) 12 - 18 18

Oral Temperature (oF): 97.8 – 99.1 96.7 (35.9 oC)

O2 Saturation (%) 95-100 100

• Upon admission the initial vitals were all within normal limits (8/12 at 00:00)

• Note: In the emergency department the vitals were similar; however the

respiratory rate was at 30 breaths/min

(MedlinePlus. 2013)

12

Initial Complete Metabolic Panel (CMP) Date (8/11 @ 2100)

Date (8/11 @ 0700) Reference Range

Sodium (mmol/L) 136-145 134 (Low)

Potassium (mmol/L) 3.5-5.1 3.6

Chloride (mmol/L) 98-107 96 (Low)

CO2 (mmol/L) 22-29 19 (Low)

Glucose (mg/dL) 74-109 79

Blood Urea Nitrogen (BUN) (mg/dL) 6-20 8

Serum Creatinine (SCr) (mg/dL) 0.50-0.90 0.60

Calcium (mg/dL) 8.6-10.0 9.6

Albumin (g/dL) 3.94-4.94 4.3

ALT (U/L) 10-35 15

AST (U/L) 10-35 17

Magnesium (mg/dL) 1.6-2.6 2.1

Phosphorus (mg/dL) 2.5-4.5 2.2 (Low)

13

Complete Blood Count and Beta-hCG (8/11 @ 2100)

Laboratory Test Reference Range Results

WBC (th/mm3) 3.2-9.9 9.7

RBC (mil/mm3) 4.28-5.19 4.90

Hemoglobin (g/dL) 12.7-16.2 14.5

Hematocrit (%) 37.0-46.0 41.7

Platelet Count (th/mm3) 127-361 253

Beta-hCG (mIU/mL) <5.0 102316 (High)

14

Urine Dipstick and Culture (8/11 @ 2100) 15

Emergency Department Course of Therapy

Upon arrival at the emergency department the following tests and examinations were utilized: Vitals, ROS, and Physical Exam Transvaginal Ultrasound Complete Metabolic Panel Complete Blood Count Beta-hCG Urine Dipstick Urine Microscopic Exam Upon completing examination, patient was agreeable to the plan of care which included admission

16

D I S E A S E O V E R V I E W

&

T R E A T M E N T S T R A T E G I E S

17

Hyperemesis Gravidarum

Nausea and Vomiting of Pregnancy (NVP)

NVP affects 70 to 85% of pregnant women

50% have both nausea and vomiting

25% have nausea only

25% are unaffected

Symptoms of NVP manifest before 9 weeks of gestation if virtually all affected women

18

(ACOG, NVP. 2004)

Hyperemesis Gravidarum

Hyperemesis Gravidarum represents the extreme end of the spectrum of NVP

Incidence 0.5 to 2%

The most common indication for admission to the hospital during the first part of pregnancy

There is no single accepted definition of hyperemesis gravidarum

19

(ACOG, NVP. 2004)

Common Hyperemesis Gravidarum Criteria

Most commonly cited criteria:

Persistent vomiting not related to other causes

A measure of acute starvation (usually large ketonuria)

Some discrete measure of weight loss (at least 5% prepregnancy weight)

Electrolyte, thyroid and liver abnormalities may be present

20

(ACOG, NVP. 2004)

Differential Diagnosis of Nausea and

Vomiting of Pregnancy

Gastrointestinal Conditions

Gastroenteritis

Gastroparesis

Achalasia

Biliary tract disease

Hepatitis

Intestinal obstruction

Peptic ulcer disease

Pancreatitis

Appendicitis

Genitourinary Tract Conditions

Pyelonephritis

Uremia

Ovarian torsion

Kidney stones

Degenerating uterine leiomyoma

Metabolic Disease

Diabetic ketoacidosis

Porphyria

Addison’s disease

Hyperthyroidism

Neurologic Disorders

Pseudotumor cerebri

Vestibular lesions

Migraines

Tumors of the central nervous system

Miscellaneous

Drug toxicity or intolerance

Psychologic

Pregnancy-Related Conditions

Acute fatty liver of pregnancy

Preeclampsia

21

(ACOG, NVP. 2004)

Etiology of Hyperemesis Gravidarum

The etiology of hyperemesis gravidarum is unknown

Other proposed ideas regarding etiology:

Conversion disorder

Inability to respond to excessive life stress

Evolutionary adaption that developed to protect the woman and her fetus from foods that might be potentially dangerous

22

(ACOG, NVP. 2004)

Etiology of Hyperemesis Gravidarum (Continued)

Hormones Human chorionic gonadotropin (hCG)

Concentrations peak with a close temporal relationship to symptoms of NVP

Estrogen

NVP is more common when estradiol levels are increased and less common when estradiol levels are decreased

Women who experience NV with estrogen from oral contraceptives are more likely to have NVP

Cigarette smoking decreases hCG and estradiol levels

Numerous studies have shown that smokers are less likely to have hyperemesis gravidarum

23

(ACOG, NVP. 2004)

Risk Factors for Hyperemesis Gravidarum

Women with increased placental mass (multiple gestation)

Family history of hyperemesis gravidarum

Patient has a prior history of hyperemesis gravidarum

Women carrying a female fetus

History of migraines or motion sickness

24

(ACOG, NVP. 2004)

Maternal Effects of NVP

In the 1930s (U.S.A.) 7 deaths were reported among 85 women with severe vomiting

Wernicke’s encephalopathy

Splenic avulsion

Esophageal rupture

Pneumothorax

Acute tubular necrosis

25

(ACOG, NVP. 2004)

Fetal Effects of NVP

Three studies have found lower birth weight (LBW) in women who did not have NVP

Numerous studies have documented lower rate of miscarriage among women with NVP compared with controls

Key Counseling Point: It is appropriate to reassure patients that the presence of NVP

even hyperemesis gravidarum most often portends well for pregnancy outcome

26

(ACOG, NVP. 2004)

Treatment Algorithm: Initial Steps 27

(ACOG, NVP. 2004)

Treatment Algorithm (Continued): No Dehydration

28

(ACOG, NVP. 2004)

Treatment Algorithm (Continued): Dehydration Present

29

(ACOG, NVP. 2004)

30 (ACOG, NVP. 2004)

Medication Safety and Efficacy

(ACOG, NVP. 2004)

31

Vitamin B6 and Doxylamine

170,000 exposures have found combination to be safe

Doxylamine and H1 Blockers

200,000 first-trimester exposures demonstrate safety

Phenothiazines

Bulk of evidence from meta-analysis indicates no teratogenicity

200,000 first-trimester exposures demonstrate safety

Medication Safety and Efficacy (Continued)

(ACOG, NVP. 2004)

32

Dopamine Antgonists and Anticholinergics

Appear safe but efficacy uncertain

Corticosteroids

Association between oral clefts and methylprednisolone use in the first trimester

Avoid use before 10 weeks gestation

Ondansetron Safety

(Pasternak B. 2013)

33

Retrospective study with 608,000 patients

Conclusions

Ondansetron taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes

O V E R V I E W O F H O S P I T A L S T A Y

A S S E S S M E N T

P L A N

D I S C H A R G E A N D F O L L O W - U P

34

Patient Hospital Course

Hospital Course Vital Signs 35

Hospital Day on 8/11 36

Medication and Strength Route Administration Frequency Indication

Morphine injection 2 mg IV 2125 Once Pain

Ondansetron 4 mg/2mL injection; 4 mg

IV 2153 Once NVP

Promethazine 12.5 mg in NaCl 0.9%, 50 mL IVPB

IV 2056, 2231 Once NVP

NaCl 0.9% bolus 1,000 mL IV 2232, 2055 Once Hydration

Note: On 8/11 to labs and exams mentioned prior to this slide were all performed

Note: Intravenous = IV PO = Oral Medication with a frequency that specifies once, that are administered more than once signifies that the same drug was ordered multiple times

Hospital Day on 8/12 37

Complete Metabolic Panel @ 0600 Pertinent findings from prior had normalized; thus labs were not

drawn henceforth

Phosphorus levels had normalized

Laboratory value: 4.1 mg/dL; Normal 2.5-4.5 mg/dL

Nothing by mouth throughout morning, began feeding later in the day

Strict ins and outs to quantify volume loss

Still experiencing nausea but feeling better

Experienced vomiting after trying to eat a grilled cheese sandwich

Hospital Day on 8/12 (Continued) 38

Medication and Strength Route Administration Time

Frequency Indication

Potassium phosphate 15 mmol in NaCl 0.9% 250 mL infusion

IV 0542 Once Hypophosphatemia

NaCl 0.9% infusion IV 0019, 0802, 0950, 1646, 2037

Continuous Hydration

Acetaminophen 650 mg tablet PO 2019 Every 6 hours PRN

Mile Pain (1-3 Pain Scale)

Ondansetron 4 mg/2mL injection; 4 mg

IV 0209, 0646, 1052, 1927

Every 4 hours PRN

NVP

Promethazine 25 mg in NaCl 0.9%, 50 mL IVPB

IV 0453, 1325, 2211 Every 4 hours PRN

NVP

Albuterol inhaler 90 mcg/actuation (Inhale 2 puffs or 180 mcg)

Inhalation Every 6 hours PRN

Asthma

Hospital Day on 8/13 39

Medication and Strength

Route Administration Time

Frequency Indication

Pyridoxine 25 mg tablet PO 0955 4 times daily NVP

NaCl 0.9% infusion IV 0153 Continuous Hydration

Ondansetron 4 mg/2mL injection; 4 mg

IV 0406 Every 4 hours PRN NVP

Promethazine 25 mg in NaCl 0.9%, 50 mL IVPB

IV 0733 Every 4 hours PRN NVP

Hospital Day on 8/13 40

Patient is tolerating light diet

Bananas, toast, and applesauce with medications

Denies vomiting throughout the night

Patient has good urine output

Education and preparation for discharge

Problem List

Hyperemesis Gravidarum

Nausea and Vomiting of Pregnancy

Hypophosphatemia

41

Assessment: Hyperemesis Gravidarum

Findings that help rule in hyperemesis gravidarum:

Intractable vomiting

Abdominal and back pain associated with vomiting

Dry mucous membranes

Ketonuria

Hypophosphatemia

Patient has experienced weight loss

Symptoms manifested before 9 weeks gestation

42

Assessment (Continued): Hyperemesis Gravidarum

Findings that help rule out other causes:

No fever or abnormal vitals

Normal WBC

Normal glucose levels

Normal liver function tests (LFTs)

Patient denies migraine or headache

Patient denies diarrhea

Patient denies urinary frequency

Abdomen is soft and non-distended

43

Assessment (Continued): Hyperemesis Gravidarum

44

Patient’s symptoms are more controlled and patient is tolerating diet

The treatment throughout the hospital stay has been appropriate

Medications have been appropriately dosed with indications that match patient’s conditions

Diet has been adequately managed and increased as tolerated

Progression towards goals of therapy

Maintaining adequate nutrition

Reduce morbidity and mortality of the patient and fetus

Pharmacologic Plan: Hyperemesis Gravidarum

(ACOG, NVP. 2004)

45

1st line therapy Pyridoxime (Vitamin B6) 10-25 mg PO TID or QID

Doxylamine 12.5 mg PO TID or QID

Maintain adequate hydration (1000 mL 0.9% NaCl continuous infusion or bolus)

2nd line therapy Promethazine 25 mg q 4 hrs PRN (Per rectum or orally)

Metoclopramide 5 to 10 mg PO q 8 hrs

Ondansetron 8 mg ODT PO q 8 hrs

Corticosteroids as a last resort Methyprednisolone 16 mg q 8 hrs PO or IV

Monitoring Plan: Hyperemesis Gravidarum

(Dugdale. 2013)

46

Monitor for signs and symptoms of dehydration Extended capillary refill time (>2 seconds) Decreased urine output (Abnormal color, delayed frequency, or <16

ounces per day) Weight loss (greater than 5 lbs.)

Monitoring for side effects of Vitamin B6 and doxylamine not

typically necessary

Ondansetron ECG, potassium, and magnesium (Based on risk factors)

Metoclopramide Signs of extrapyramidal symptoms and tardive dyskinesia

Assessment and Plan for Hypophosphatemia 47

Assessment:

Hypophosphatemia upon admission secondary to emesis (Levels: 2.2 mg/dL; Normal: 2.5 to 4.5 )

Plan

Resolution of hypophosphatemia was resolved after 15 mmol administration of phosphorus (4.1 mg/dL)

Manage NVP as outlined in Hyperemesis Gravidarum plan

Asthma Assessment

(ACOG Asthma. 2008)

48

Asthma is the patient’s only reported chronic condition

The amount of information provided in the patient’s progress notes regarding asthma management is extremely limited

The patient did not complain of any symptoms in relation to asthma throughout her hospital stay

Patient did not utilize any dose of his albuterol rescue inhaler

Asthma Plan

(ACOG Asthma. 2008)

49

Inhaled albuterol is recommended rescue therapy for pregnant women with Asthma

Continue to use as need albuterol

At 12 week gestation follow-up (2 weeks from now) assess asthma

Access how many doses of albuterol have been utilized

Pulmonary physiologic assessment

FEV1 and oxygen saturation (FEV1 > 70% and SPO2 > 95)

Discharge Medication

Ondansetron 8 mg orally disintegrating tablet

Take 1 tablet (8 mg) by mouth every 8 (eight) hours as needed for nausea; for up to 20 doses

Promethazine 12.5 mg suppository

Place 2 suppositories (25 mg total) rectally every 4 hours as needed for nausea. For up to 15 doses

50

Discharge Medications (Continued)

Continue taking the following medications:

Doxylamine-Pyridoxine 10-10 mg tablet Take 20 mg by mouth daily. Take 2 tabs at bedtime, if

symptoms persist increase to 4 tabs at bedtime for 30 days

Albuterol 2.5 mg/3mL nebulizer solution

Take 3 mLs (2.5 mg total) by nebulization every 6 (six) hours as needed for wheezing

Albuterol 90 mcg/actuation inhaler

Inhale 1-2 puffs into the lungs every 6 (six) hours as needed for wheezing

51

Discharge Plan and Follow-Up

Use doxylamine-pyridoxine first line for NVP

Ondansetron and promethazine are second line for patient’s NVP

Education to maintain adequate fluid intake and appropriate diet

Establish care with UW Family Medicine

Establish appointment 2 weeks from discharge

(12 weeks gestation)

Resident with knowledge of patient history will be an appropriate provider (monitor NVP and asthma as discussed previously)

52

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Questions???

References

MedlinePlus. Vital Signs. Last updated: 2013 Jan 1. Accessed 2015 Aug 19. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/002341.htm.

The American College of Obstetricians and Gynecologists. Nausea and vomiting of pregnancy. ACOG Practice Bulletin. Clinical Management Guidelines for Obstetrician-Gynecologists. Number 52. April 2004.

Pasternak B, Svanström H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med. 2013 Feb 28;368(9):814-23. doi: 10.1056/NEJMoa1211035. Erratum in: N Engl J Med. 2013 May 30;368(22):2146. PubMed PMID: 23445092. Accessed 2015 Aug 19. Available from: http://www.nejm.org/doi/full/10.1056/NEJMoa1211035.

The American College of Obstetricians and Gynecologists. Asthma in Pregnancy. ACOG Practice Bulletin. Number 90. February 2008.

Dugdale DC. Capillary nail refill test. MedlinePlus. Last Updated: 2013 April 4. Accessed on 2015 Aug 20. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/003394.htm .

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