GTG 69 NVP & Hyperemesis Gravidarum

This is the summary of GTG -69 Hyperemesis Gravidarum released in 2016. This is one of a frequently tested guideline in the exam. Nausea and vomiting of pregnancy is one the most common indication for admission with typical stay of 3-4 days in the Hopsital. Hyperemesis Gravidarum is the severe form of NVP which can adversely affect the QoL and has a high recurrence in next pregnancy. 

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Epidemiology

NVP symptoms of nausea ± vomiting during early pregnancy where no other causes 80%

HG severe form of NVP 0.3-3.6%

Recurrence 15%-80% 

• Reduced if change in paternity in second pregnancy 10.9%

Diagnosis of NVP & HG

NVP diagnosis  ONLY when onset in 1st trimester + other causes excluded 

• If after 10+6 wk→ consider other causes 
• Typically starts 4-7th wk Peaks 9th wk Resolves by 20 wk in 90%

HG diagnosis Protracted NVP with triad of >5% pre-pregnancy weight loss, dehydration & electrolyte imbalance

Severity NVP classify Objective & validated index of N & V PUQE Pregnancy Unique Quantification of Emesis

Initial clinical assessment & baseline investigations

• Features in history, examination & investigations to asses & diagnose NVP and HG for monitoring of the severity

History and Examination

Investigations

Urine dipstick quantify ketonuria as 1+ or more MSU

U&E hypo/hyperkalemia, hyponatremia, dehydration, renal disease

FBC infections, anemia, HCT

Blood glucose monitoring exclude DK if diabetic

USG confirm viability exclude multiple pregnancy & GTN

If refractory or h/o previous admission check TFT, LFT, Ca & Phosphate, Amylase, ABG

NVP & HG associated with 

• Hyponatremia, hypokalaemia, low serum urea, including HCT & ketonuria→metabolic hypochloraemic alkalosis
• If severe→ metabolic acidaemia 

TFT  abnormal in up to 2/3 of HG 60%

• Biochemical thyrotoxicosis
• ↑free T4 ± suppressed TSH
• Clinically euthyroid
• Thyroid antibody rare
• Usually resolve as HG improve
• No need for thyroid drugs

LFT abnormal in up to 40% of HG

• Most likely ↑ transaminases
• Bilirubin slightly ↑ but no jaundice
• Amylase mild ↑
• All improve as HG improve

Differential diagnosis

• Peptic ulcer
• Cholecystitis
• Gastroenteritis
• Hepatitis
• Pancreatitis
• UTI or Pylonephritis
• Metabolic
• Neurological
• Drug-induced

Severe abdominal or epigastric pain unusual in NVP & HG→ warrant further investigations S amylase & USG

Gastroduodenoscopy Safe in pregnancy

Chronic infection with H.pylori Consider testing antibodies

Initial Management of NVP & HG

How woman should be managed? Main antiemetics, fluid replacement Thiamine

Mild NVP in community with antiemetics

Primary/community management fails or PUQE <13 Ambulatory day care management

Consider inpatient if any ONE of this

• Continued N&V → unable to keep down oral antiemetics
• Continued N&V + ketonuria ± wt loss >5% pre-pregnancy despite oral antiemetics
• Confirmed or suspected comorbidity (UTI, oral antibiotic intolerance)

Ambulatory day care provides parenteral fluid, vitamins & antiemetics

• Associated with high pt satisfaction
• Ambulatory s/c metoclopramide → 89.3% effective

Recurrent NVP & HG despite ambulatory daycare management inpatient especially if electrolyte imbalance or nutritional deficiencies

Therapeutic options

Antiemetics

• First line  Antihistamines & Phenothiazines→ safe
• Use combination if do not respond to single
• With severe or persistent HG parental or rectal route is more effective than oral
• Drug-induced extrapyramidal symptoms & oculogyric crises with use of phenothiazine & metoclopramide promptly stop drug
• Clinicians should use antiemetics with which they are familiar
• Use different classes of drug if one not effective

Metoclopramide 

• Safe & effective but extrapyramidal symptoms so use as 2nd line
• Only prescribe short-term
• 30mg/day or 0.5mg/kg in 24 hrs  I/V → slow bolus inj over at least 3 min
• Maximum duration 5 days

Ondansetron

Safe & effective but limited data so use as 2nd line

Use should be limited to those not adequately management by other antiemetics & preferably after 1st trimester

Better at reducing N&V than doxylamine & pyridoxine

Equally effective but with less side effects than metoclopramide

More effective than metoclopramide in reducing severe vomiting

Safe drugs with no ↑ teratogenesis risk or other adverse effects

• Antihistamines promethazine, cyclizine, cinnarizine, doxylamine, dimenhydrinate 
• Phenothiazines prochlorperazine, chlorpromazine, perphenazine
• Dopamine antagonist metoclopramide, domperidone

Pyridoxine

• Not recommended for NVP & HG
• Combination with doxylamine more effective than pyridoxine alone

Corticosteroids

• Reserved when standard therapies fail
• Rapid & dramatic improvements in women with refractory HG
• Daily I/V hydrocortisone 300mg → superior to I/V metoclopramide in reducing vomiting & recurrence
• Suggested dose 100mg I/V BD, once improved convert to 40-50 mg prednisolone daily, then taper off until lowest maintenance dose with controlled symptoms

Diazepam

• Not recommended
• Addition of diazepam reduces nausea but no difference in vomiting

Best Rehydration Regimen

• N.Saline + KCl in each bag + administration guided by daily electrolyte monitoring→ most appropriate I/V rehydration
• Dextrose do not give unless serum Na normal & thiamine given before (high doses 100mg/day parental to prevent Wernick's Encephalopathy)

Complementary therapies

Ginger

• May be used in mild to moderate NVP (multiple studies). 
• No studies for ginger use in HG
• No ↑ risk of major malformations
• Potential maternal adverse effects anticoagulant effect, stomach irritation, potential interaction with ß blockers & benzodiazepines

Acustimulations--acupressure & acupuncture

• Reassure acustimulation safe in pregnancy
• Acupressure may improve NVP
• At pericardium 6 located about 2.5 fingers breadth up from wrist crease on inside of forearm b/w Palmaris Longus & Felxor Carpi Radialis tendon

Hypnosis

• Not recommended

Monitoring & adverse effects

Daily urea & electrolytes in pt on I/V fluids to prevent & treat hyponatremia & hypokalaemia

H2 antagonist or PPI in gastritis, reflux esophagitis. 

Oesophageal gastroduodenoscopy safe, indicated if haematemesis or severe epigastric pain

Thiamine (oral or i/v) to ALL admitted with prolonged vomiting & especially before giving dextrose or parenteral nutrition

Wernick's Encephalopathy

• Vit B1 deficiency
• Classically presents with blurred vision, unsteadiness & confusion/memory problem/drowsiness
• On examination nystagmus, ophthalmoplegia, hyporeflexia or areflexia, gait ± finger-nose ataxia
• In HG episodic & slow onset
• Potentially fatal but reversible medical emergency
• Complete remission 29%
• Overall pregnancy loss 48% —including IUDs & TOP

Thromboprophylaxis LMWH in admitted with HG

• Continue for at least til 1st trimester
• OR for VTE with HG  2.5
• Adjusted OR of DVT  4.4

Previous or current NVP or HG Consider avoiding iron preparation —2/3 improvement

Further Management

Role of MDT

• Midwives, nurses, dietician, pharmacists, endocrinologist, nutritionists, gastroenterologists & mental health team including psychiatrists
• Mental health team involvement may improve QoL & ability to cope with pregnancy

Parenteral nutrition & feto-maternal risks

• Consider parenteral when all other medical therapies have failed after discussion at MDT
• No defined criteria
• Effectiveness not well established
• Often employed as last resort
• Enteral feeding options nasogastric, naso-duodenal or naso-jejunal tubes or percutaneous endoscopic gastrostomy or jejunostomy feeding
• Peripherally inserted central catheter PICC line parenteral feeding better tolerated than enteral feeding but high risk of infection & vascular perforation
• Intra-gastric feeding ok for short term but ↑ risk of N&V
• Naso-jejunal tube put endoscopically to jejunum & continuous infusion for feeding. Great improvements within 48hr
• Percutaneous endoscopic gastrojejunostomy feeding  under GA in 2nd trimester effective, safe & well-tolerated. 
• TPN  complex high-risk intervention
• Useful in refractory cases to ensure adequate calorie intake
• Only a last resort because expensive, inconvenient, associated with serious complications like thrombosis, infection & metabolic disturbances 
• Associated with↓ perinatal mortality
• Strict protocol with careful monitoring essential

When should TOP be considered?

• All therapeutic measure should have been tried before offering TOP of a wanted pregnancy 
• Consider all t/m options before decision
• Psychiatrist opinion should be sought
• Decision at MDT with documentation of therapy failure
• Counselling before & after the decision

Prominent reasons

• 66% unable to maintain self & family care
• 51% fear of baby or self dying
• 22% think baby would be abnormal

Discharge & follow-up

• Individualised management plans
• If NVP & HG continued in late 2nd or 3rd trimester offer serial growth scans
• Patient support groups
• Follow-up appointment
• Psychological & social support

Complications in Pregnancy

• HG & low pregnancy wt gain ↑ risk of preterm delivery & LBW
• Excessive vomiting lasting beyond 5M associated with underweight children
• Repeated admission 18% incidence for SGA & LBW

Effect of NVP & HG in postnatal time

• Advice about risk of recurrence 15 – 81%
• Early lifestyle/diet modification & antiemetics which were useful in index pregnancy advisable to reduce NVP & HG in current pregnancy

Effects of NVP & HG on QoL

Women with HG 

• 3-6 times more likely than NVP to have low QoL
• Persistent nausea most adversely affect QoL
• significantly higher somatisation, depression, anxiety & overall psychological distress even when HG resolved to mild NVP
• Symptoms of major depression associated with moderate & severe NVP but prior h/o depression not a determinant
• More depression & anxiety if they feel that healthcare professional is unsympathetic

Having support from at least 3 other persons  protective for NVP

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