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ob.hyperemesis-gravidarum.v1

Hyperemesis Gravidarum

obstetricsacuteadultpregnancy
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Detailed

Hyperemesis gravidarum (HG) = the severe end of the NVP spectrum: intractable first-trimester nausea/vomiting + ≥ 5 % prepregnancy weight loss + dehydration + ketonuria/electrolyte disturbance, after exclusion of other causes (ACOG PB 189). Partition NVP-mild/moderate (PUQE ≤ 12; outpatient first-line antiemetics) vs HG (PUQE ≥ 13 OR ≥ 5 % weight loss + dehydration + ketonuria), and within HG: uncomplicated vs Wernicke-encephalopathy risk vs electrolyte derangement (hypokalemia / hyponatremia / hypochloremic alkalosis) vs refractory/enteral-or-parenteral-nutrition-dependent. Mimics that must be excluded before anchoring: gestational trophoblastic disease (molar) and gestational transient thyrotoxicosis. Distinct from later-onset nausea of pre-eclampsia/HELLP (ob.pre-eclampsia.core.v1).

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GA + weight-loss percentage documented; NVP-vs-HG and HG sub-phenotype tier assigned

Patient inputs (22)

Frequency + retching feed the PUQE severity score (≤ 6 mild / 7-12 moderate / ≥ 13 severe)

Inability to tolerate any oral intake drives IV rehydration + admission vs ambulatory day-case management

Multifetal gestation increases β-hCG and HG severity/duration; also raises the prior probability of the molar/multifetal differential

Pre-existing thyroid disease (Graves vs gestational transient thyrotoxicosis), diabetes (DKA mimic + euglycemic risk), or GI disease modifies the differential and antiemetic/fluid choices

Tachycardia supports dehydration severity; disproportionate tachycardia + tremor + heat intolerance suggests thyrotoxicosis mimic

Orthostatic hypotension grades dehydration; new HTN + proteinuria in 2nd/3rd trimester with nausea is pre-eclampsia, not HG

HG typically presents 4-9 wk, peaks ~ 9 wk, resolves by ~ 20 wk in ~ 90 %; new or persistent severe vomiting after ~ 9-10 wk or first onset > 9 wk lowers HG pretest probability and raises mimic suspicion; corticosteroid use is reserved for refractory disease > 10 wk

≥ 5 % loss of prepregnancy body weight is the defining HG criterion and tracks severity/response

Ketonuria + concentrated urine supports HG dehydration and guides rehydration endpoint (ketone clearance)

Hypokalemia, hyponatremia, hypochloremic metabolic alkalosis (protracted vomiting) vs ketotic picture; renal function; guides KCl + cautious Na correction

Suppressed TSH + elevated fT4 = gestational transient thyrotoxicosis (hCG-mediated; antithyroid drugs NOT indicated) vs Graves (TRAb, goiter, ophthalmopathy)

Hemoconcentration supports dehydration severity; leukocytosis raises an infective mimic

Rule out UTI/pyelonephritis as a vomiting trigger and PPROM-unrelated infective mimic

Confirm intrauterine viable singleton vs multifetal vs molar (snowstorm/theca-lutein cysts) — molar disease is a key HG mimic

Serial weight tracks ≥ 5 % loss criterion and response to therapy

Postural HR/BP change quantifies volume depletion and guides IV bolus volume

Fever points away from uncomplicated HG toward an infective mimic (pyelonephritis, gastroenteritis, appendicitis) or thyroid storm

Current antiemetic step + QTc-prolonging co-medications gate ondansetron/metoclopramide escalation and ECG monitoring

Recurrence ~ 15-80 % in subsequent pregnancy; informs early prophylactic antiemetics + preconception counseling

Mild transaminitis can occur in HG itself; marked elevation / elevated lipase points to hepatitis / pancreatitis / HELLP mimics

Markedly elevated β-hCG raises molar/multifetal and gestational-transient-thyrotoxicosis probability; trend interpreted with US

Promethazine/metoclopramide intolerance or extrapyramidal reaction redirects the antiemetic ladder

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Severity triggers (7)

7 need judgement
  • informationallife_threateninghg_wernicke_encephalopathy_risk
    Wernicke-encephalopathy risk/features — prolonged HG vomiting (especially if dextrose/PN given without prior thiamine) OR confusion/ataxia/ophthalmoplegia → treatment-dose IV thiamine IMMEDIATELY and before any further dextrose; neurology + critical care (Chiossi 2006 PMID 16735862; RCOG GTG 69 2024).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehg_with_weight_loss_dehydration_ketonuria
    Hyperemesis gravidarum — intractable first-trimester vomiting + ≥ 5 % prepregnancy weight loss + dehydration + ketonuria (± PUQE ≥ 13) → IV isotonic rehydration with KCl as needed, thiamine BEFORE any dextrose, antiemetic-ladder escalation, day-case vs admission per severity (ACOG PB 189; RCOG GTG 69 2024).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehg_electrolyte_derangement
    Electrolyte-derangement HG — hypokalemia (severe if < 2.5 mmol/L), hyponatremia, or hypochloremic metabolic alkalosis from protracted vomiting → monitored correction: KCl replacement with cardiac monitoring; correct hyponatremia CAUTIOUSLY to avoid osmotic demyelination (RCOG GTG 69 2024).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehg_refractory_nutrition_dependent
    Refractory / nutrition-dependent HG — failure of optimised antiemetic ladder + rehydration → reassess corticosteroid eligibility (methylprednisolone ONLY if refractory and > 10 wk gestation) and escalate nutrition: enteral (NG/NJ) tube feeding → PPN/TPN as last resort; VTE prophylaxis while admitted (Boelig Cochrane PMID 27091683; ACOG PB 189; RCOG GTG 69 2024).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverehg_molar_pregnancy_mimic
    Gestational trophoblastic disease mimic — markedly elevated β-hCG and/or molar appearance on US with HG features → GTD pathway (uterine evacuation + post-molar β-hCG surveillance); HG typically resolves after evacuation (ACOG PB 189 differential).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatehg_gestational_transient_thyrotoxicosis_mimic
    Gestational transient thyrotoxicosis mimic — suppressed TSH + elevated fT4 with HG features, no goiter/ophthalmopathy/TRAb → supportive care only; antithyroid drugs NOT indicated (hCG-mediated, self-limited, normalises as hCG falls). TRAb-positive/goiter/ophthalmopathy → Graves workup (ATA gestational thyroid guidance).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildnvp_mild_moderate_outpatient
    Mild-moderate NVP — PUQE ≤ 12 without ≥ 5 % weight loss, dehydration, or ketonuria → outpatient first-line antiemetics (pyridoxine ± doxylamine, then antihistamine/phenothiazine rung) + dietary measures. Not the acute HG pathway.
    Trigger could not be auto-evaluated — needs clinician judgement.

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Recommended regimen

Hyperemesis gravidarum management axis — antiemetic ladder + rehydration/electrolytes + thiamine-before-dextrose + nutrition escalation (ACOG PB 189 + RCOG GTG 69 2024 + SOGC + Boelig Cochrane PMID 27091683)
axis: hyperemesis_managementstep antiemetic_ladder_first_line - First-line antiemetic — pyridoxine ± doxylamine (ACOG PB 189; SOGC)
Selected step "First-line antiemetic — pyridoxine ± doxylamine (ACOG PB 189; SOGC)" — NVP/HG requiring pharmacologic control — first rung; start before escalation
  • pyridoxine
    first line
    vitamin_b6
    10-25 mg PO q6-8h • PO • q6-8h
    triggers: nvp_or_hg_requiring_pharmacologic_control
    ACOG PB 189 first-line; pyridoxine reduces nausea severity; well-tolerated; combine with doxylamine for added benefit
    rxcui 203164
  • doxylamine
    first line
    antihistamine_h1
    12.5 mg PO (with pyridoxine; up to QID, larger evening dose) • PO • q6-8h (often larger HS dose)
    triggers: nvp_or_hg_requiring_pharmacologic_control
    ACOG PB 189 first-line in fixed/loose combination with pyridoxine; Category A pregnancy safety; sedation is the main limiting effect
    rxcui 3642

outpatient playbook — drug actions (3)

  1. 1. pyridoxine ± doxylamine first-line
    rxcui 203164
    pyridoxine 10-25 mg PO q6-8h ± doxylamine 12.5 mg PO • PO • q6-8h
    trigger: Mild-moderate NVP or HG step-down
    ACOG PB 189 first-line; taper as symptoms resolve (most resolve by ~ 20 wk)
  2. 2. add antihistamine/phenothiazine or metoclopramide/ondansetron if inadequate
    rxcui 6915
    per ladder • PO • per agent
    trigger: Inadequate control on first-line
    ACOG PB 189 ladder; counsel risk-benefit for ondansetron
  3. 3. day-case IV rehydration for moderate disease
    NS/LR + KCl as needed; thiamine before any dextrose • IV • as needed
    trigger: Moderate dehydration/ketonuria, tolerating some oral
    RCOG GTG 69 2024 ambulatory day-case pathway

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Persistent / intractable nausea and vomiting beginning in the first trimester not relieved by first-line oral antiemetics (ACOG PB 189); ≥ 5 % loss of prepregnancy body weight attributable to vomiting — defining HG criterion (ACOG PB 189; RCOG GTG 69 2024); Ketonuria on urine dipstick with clinical dehydration — supports HG vs mild-moderate NVP (ACOG PB 189).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Hyperemesis Gravidarum** (ob.hyperemesis-gravidarum.v1).
Phenotype framing: Mild-moderate NVP (no weight loss/dehydration/ketonuria — outpatient antiemetics, not this pathway); gestational trophoblastic disease / molar pregnancy (β-hCG + US); multifetal gestation (higher β-hCG, more severe/prolonged NVP); gestational transient thyrotoxicosis (TSH/fT4; self-limited, hCG-mediated) vs Graves disease (TRAb, goiter, ophthalmopathy); thyroid storm; diabetic ketoacidosis incl. euglycemic (glucose, anion gap, ketones); acute pancreatitis (lipase); hepatitis / HELLP (LFTs, BP, platelets); pyelonephritis / UTI (UA + culture); gastroenteritis / appendicitis (fever, localised pain); raised intracranial pressure / CNS lesion (headache, neuro deficit, papilledema); medication or substance effect.
Scope: Hyperemesis gravidarum (HG) = the severe end of the NVP spectrum: intractable first-trimester nausea/vomiting + ≥ 5 % prepregnancy weight loss + dehydration + ketonuria/electrolyte disturbance, after exclusion of other causes (ACOG PB 189). Partition NVP-mild/moderate (PUQE ≤ 12; outpatient first-line antiemetics) vs HG (PUQE ≥ 13 OR ≥ 5 % weight loss + dehydration + ketonuria), and within HG: uncomplicated vs Wernicke-encephalopathy risk vs electrolyte derangement (hypokalemia / hyponatremia / hypochloremic alkalosis) vs refractory/enteral-or-parenteral-nutrition-dependent. Mimics that must be excluded before anchoring: gestational trophoblastic disease (molar) and gestational transient thyrotoxicosis. Distinct from later-onset nausea of pre-eclampsia/HELLP (ob.pre-eclampsia.core.v1).

No severity triggers fired against current inputs.

Plan

Regimen axis: **Hyperemesis gravidarum management axis — antiemetic ladder + rehydration/electrolytes + thiamine-before-dextrose + nutrition escalation (ACOG PB 189 + RCOG GTG 69 2024 + SOGC + Boelig Cochrane PMID 27091683)** — step "First-line antiemetic — pyridoxine ± doxylamine (ACOG PB 189; SOGC)".
1. pyridoxine 10-25 mg PO q6-8h PO q6-8h (vitamin_b6, first line) — ACOG PB 189 first-line; pyridoxine reduces nausea severity; well-tolerated; combine with doxylamine for added benefit
2. doxylamine 12.5 mg PO (with pyridoxine; up to QID, larger evening dose) PO q6-8h (often larger HS dose) (antihistamine_h1, first line) — ACOG PB 189 first-line in fixed/loose combination with pyridoxine; Category A pregnancy safety; sedation is the main limiting effect

Setting playbook (outpatient) — Mild-moderate NVP and post-acute HG follow-up — first-line antiemetics + dietary measures, day-case rehydration for moderate disease tolerating some oral intake, weight/nutrition recovery, mental-health screen, recurrence + preconception counseling
3. pyridoxine ± doxylamine first-line pyridoxine 10-25 mg PO q6-8h ± doxylamine 12.5 mg PO PO q6-8h — Mild-moderate NVP or HG step-down (ACOG PB 189 first-line; taper as symptoms resolve (most resolve by ~ 20 wk))
4. add antihistamine/phenothiazine or metoclopramide/ondansetron if inadequate per ladder PO per agent — Inadequate control on first-line (ACOG PB 189 ladder; counsel risk-benefit for ondansetron)
5. day-case IV rehydration for moderate disease NS/LR + KCl as needed; thiamine before any dextrose IV as needed — Moderate dehydration/ketonuria, tolerating some oral (RCOG GTG 69 2024 ambulatory day-case pathway)

Non-pharmacologic actions:
- Dietary measures — small frequent bland meals, ginger, avoid triggers
- Dietitian follow-up for weight recovery
- Preconception plan for early prophylactic pyridoxine ± doxylamine + early presentation next pregnancy
- Mental-health referral if EPDS elevated / decisional regret

AVOID / contraindication checks:
- Thiamine MUST precede any dextrose or parenteral nutrition in prolonged HG Wernicke prophylaxis (Chiossi 2006 PMID 16735862; RCOG GTG 69 2024)
- Correct hyponatremia cautiously avoid osmotic demyelination syndrome (RCOG GTG 69 2024)
- Cardiac monitoring for IV KCl replacement in severe hypokalemia
- Ondansetron counsel limited first trimester data and QTc caution correct K and Mg first avoid high IV doses (Pasternak 2013 PMID 23488728; Huybrechts 2018 PMID 30561479)
- Metoclopramide limit cumulative duration 12 weeks tardive dyskinesia risk (FDA labeling)
- Corticosteroids reserved for refractory HG and only after 10 weeks gestation oral cleft signal (Boelig Cochrane PMID 27091683; ACOG PB 189)
- Promethazine IV must be diluted and slow severe tissue injury with extravasation (FDA labeling)
- Antithyroid drugs NOT indicated for gestational transient thyrotoxicosis hCG mediated self limited (ATA gestational thyroid guidance)
- VTE thromboprophylaxis LMWH when admitted immobile or dehydrated with HG (RCOG GTG 69 2024)
- Parenteral nutrition is last resort line sepsis and thrombosis risk prefer enteral (ACOG PB 189)

Monitoring

Regimen monitoring:
- Serial weight toward recovery of the ≥ 5 % prepregnancy loss
- Daily urine ketones + specific gravity as rehydration endpoint
- Serial electrolytes/BMP during IV therapy — K+ + Na+ trend (cautious Na correction rate)
- Fluid balance + symptom/PUQE re-scoring each review
- Neuro checks if Wernicke risk or after dextrose exposure
- ECG/QTc if ondansetron/metoclopramide/chlorpromazine used, especially with hypokalemia/hypomagnesemia
- Thyroid re-check only if persistently abnormal (gestational transient thyrotoxicosis should normalise as hCG falls)
- Glucose monitoring if corticosteroids used or pre-existing diabetes
- VTE-prophylaxis adherence while admitted

Setting (outpatient) monitoring:
- Weight recovery + PUQE at follow-up visits
- Re-check thyroid only if it had not normalised
- Taper antiemetics as tolerated (most resolve by ~ 20 wk)

Follow-up plan: Outpatient obstetric follow-up with continued/step-down antiemetics (most HG resolves by ~ 20 wk; a minority persist to term — plan a taper as tolerated). Nutrition / weight-recovery monitoring + dietitian follow-up. Mental-health screen (anxiety, depression, decisional regret, post-traumatic stress; consider EPDS) — HG carries a substantial psychological burden. Recurrence counseling: ~ 15-80 % in a subsequent pregnancy → preconception plan for early prophylactic pyridoxine ± doxylamine and early presentation. Thiamine repletion documented if any dextrose/parenteral nutrition was given. Re-check thyroid only if it had not normalised.
- Close-out criterion: Symptoms controlled on outpatient regimen; weight recovering; mental-health + recurrence + nutrition counseling delivered

Monitoring phase: Serial weight (toward recovery of the ≥ 5 % loss) + daily urine ketones (rehydration endpoint) + serial electrolytes/BMP during IV therapy (K+, Na+ trend; cautious Na correction rate) + fluid balance + symptom/PUQE re-scoring. Neuro checks if Wernicke risk or after dextrose exposure. ECG/QTc if ondansetron/metoclopramide/chlorpromazine used (especially with hypokalemia/hypomagnesemia). Thyroid re-check only if persistently abnormal (gestational transient thyrotoxicosis should normalise as hCG falls). Glucose monitoring if corticosteroids or diabetes. VTE-prophylaxis adherence while admitted.

Disposition

Current setting: outpatient — Mild-moderate NVP and post-acute HG follow-up — first-line antiemetics + dietary measures, day-case rehydration for moderate disease tolerating some oral intake, weight/nutrition recovery, mental-health screen, recurrence + preconception counseling

Disposition criteria:
- Symptoms controlled on oral regimen + weight recovering + mental-health stable → routine antenatal care + recurrence counseling

Escalation triggers (move to higher acuity):
- Recurrent dehydration/ketonuria not controlled by day-case → admission
- New Wernicke/neurologic features → urgent care + IV thiamine
- Worsening mental-health crisis → urgent mental-health referral

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Wernicke-encephalopathy risk/features — prolonged HG vomiting (especially if dextrose/PN given without prior thiamine) OR confusion/ataxia/ophthalmoplegia → treatment-dose IV thiamine IMMEDIATELY and before any further dextrose; neurology + critical care (Chiossi 2006 PMID 16735862; RCOG GTG 69 2024).
- [SEVERE] Hyperemesis gravidarum — intractable first-trimester vomiting + ≥ 5 % prepregnancy weight loss + dehydration + ketonuria (± PUQE ≥ 13) → IV isotonic rehydration with KCl as needed, thiamine BEFORE any dextrose, antiemetic-ladder escalation, day-case vs admission per severity (ACOG PB 189; RCOG GTG 69 2024).
- [SEVERE] Electrolyte-derangement HG — hypokalemia (severe if < 2.5 mmol/L), hyponatremia, or hypochloremic metabolic alkalosis from protracted vomiting → monitored correction: KCl replacement with cardiac monitoring; correct hyponatremia CAUTIOUSLY to avoid osmotic demyelination (RCOG GTG 69 2024).

Citations

- ACOG Practice Bulletin 189 (2018, reaffirmed) Nausea and Vomiting of Pregnancy + RCOG Green-top Guideline 69 (2024) The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum + SOGC NVP Clinical Practice Guideline + ATA gestational thyroid guidance (gestational transient thyrotoxicosis) + Koren PUQE validation (PMID 16100620; PMID 12066075) + Boelig Cochrane interventions for HG (PMID 27091683) + Pasternak NEJM 2013 (PMID 23488728) + Huybrechts JAMA 2018 (PMID 30561479) ondansetron first-trimester safety + Chiossi Wernicke-in-HG systematic review (PMID 16735862) [PMID:16100620](https://pubmed.ncbi.nlm.nih.gov/16100620/)
- Cited evidence (PMID 12066075) [PMID:12066075](https://pubmed.ncbi.nlm.nih.gov/12066075/)
- Cited evidence (PMID 27091683) [PMID:27091683](https://pubmed.ncbi.nlm.nih.gov/27091683/)
- Cited evidence (PMID 23488728) [PMID:23488728](https://pubmed.ncbi.nlm.nih.gov/23488728/)
- Cited evidence (PMID 30561479) [PMID:30561479](https://pubmed.ncbi.nlm.nih.gov/30561479/)

Last reconciled with current guidelines: 2026-05-15.
References
  • ACOG Practice Bulletin 189 (2018, reaffirmed) Nausea and Vomiting of Pregnancy + RCOG Green-top Guideline 69 (2024) The Management of Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum + SOGC NVP Clinical Practice Guideline + ATA gestational thyroid guidance (gestational transient thyrotoxicosis) + Koren PUQE validation (PMID 16100620; PMID 12066075) + Boelig Cochrane interventions for HG (PMID 27091683) + Pasternak NEJM 2013 (PMID 23488728) + Huybrechts JAMA 2018 (PMID 30561479) ondansetron first-trimester safety + Chiossi Wernicke-in-HG systematic review (PMID 16735862) — PMID:16100620
  • Cited evidence (PMID 12066075) — PMID:12066075
  • Cited evidence (PMID 27091683) — PMID:27091683
  • Cited evidence (PMID 23488728) — PMID:23488728
  • Cited evidence (PMID 30561479) — PMID:30561479