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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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