12-phase flow (12)

1. 1FRAME
   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).
   inputs: gestational_age_weeks, prepregnancy_weight_and_current_weight
   advance: GA + weight-loss percentage documented; NVP-vs-HG and HG sub-phenotype tier assigned
2. 2ENTRY
   Recognise HG via intractable first-trimester vomiting + ≥ 5 % prepregnancy weight loss + dehydration + ketonuria, OR a PUQE-severe presentation, OR a red-flag entry (Wernicke features; inability to tolerate any oral intake; suppressed TSH + elevated fT4; markedly elevated β-hCG / molar US). Mild-moderate NVP (PUQE ≤ 12, no weight loss/dehydration) routes to outpatient first-line antiemetics rather than this acute pathway.
   inputs: gestational_age_weeks
   advance: HG suspected; severity-defining feature (weight loss / dehydration / ketonuria / PUQE-severe / Wernicke) documented
3. 3CONTEXT
   GA exact + prepregnancy vs current weight + vomiting frequency/duration (PUQE inputs) + oral-intake tolerance + prior HG history (recurrence ~ 15-80 %) + multifetal status (raises β-hCG + molar prior) + pre-existing thyroid/diabetes/GI disease + current antiemetic step + QTc-risk co-medications + antiemetic allergy/intolerance + maternal HR/BP. Critical decision context for PUQE severity, antiemetic-ladder rung, admission vs day-case, and which mimics to actively exclude.
   inputs: duration_and_frequency_of_vomiting, oral_intake_tolerance, prior_hg_in_prior_pregnancy, multifetal_gestation_status, preexisting_thyroid_or_diabetes_or_gi_disease, maternal_hr, maternal_bp
   advance: Severity + risk-factor + comorbidity context captured; PUQE inputs available
4. 4RED_FLAGS
   Wernicke encephalopathy features (confusion / ataxia / ophthalmoplegia) → treatment-dose IV thiamine IMMEDIATELY and BEFORE any dextrose (Chiossi 2006 PMID 16735862). Severe dehydration / orthostatic collapse / oliguria → urgent IV isotonic resuscitation. Severe hypokalemia (< 2.5 mmol/L) or symptomatic hyponatremia → monitored electrolyte correction (cautious Na rate to avoid osmotic demyelination; cardiac monitoring for K+ replacement). Thyroid-storm features (fever + marked tachyarrhythmia + agitation on a thyrotoxic background) → critical-care + endocrine, escalate via maternal sepsis/septic-shock protocol if hemodynamically unstable. Marked transaminitis / RUQ pain / new HTN + proteinuria in 2nd-3rd trimester → pre-eclampsia/HELLP route (ob.pre-eclampsia.core.v1), not HG.
   inputs: orthostatic_vitals, maternal_temperature, confusion_ataxia_ophthalmoplegia_wernicke
   actions: protocol.septic_shock
   advance: Red-flag decisions documented (thiamine-before-dextrose, severe-dehydration resuscitation, severe-electrolyte correction, thyroid-storm/PE routing)
5. 5INITIAL_WORKUP
   Urine dipstick (ketones + specific gravity), serum electrolytes/BMP (hypokalemia, hyponatremia, hypochloremic metabolic alkalosis, renal function), TSH + free T4 (gestational transient thyrotoxicosis vs Graves), CBC (hemoconcentration; leukocytosis = infective mimic), LFTs + lipase if atypical (hepatitis / pancreatitis / HELLP), urinalysis + culture (UTI/pyelonephritis), quantitative β-hCG, and obstetric ultrasound for viability + multifetal + molar screen. Establish the ≥ 5 % weight-loss baseline and ketone-clearance rehydration endpoint.
   inputs: urine_ketones_and_specific_gravity, serum_electrolytes_bmp, tsh_and_free_t4, cbc_with_hematocrit, urinalysis_and_urine_culture, obstetric_ultrasound_viability_and_molar_screen
   actions: panel.cbc, panel.renal
   advance: Diagnostic labs + urinalysis + obstetric US obtained; electrolyte + thyroid + molar status known
6. 6BRANCHING_WORKUP
   Branch by HG sub-phenotype + mimic status. (a) Suppressed TSH + elevated fT4 without goiter/ophthalmopathy/TRAb → gestational transient thyrotoxicosis: supportive care only, antithyroid drugs NOT indicated, resolves with hCG decline; TRAb-positive / goiter / ophthalmopathy → Graves workup. (b) Markedly elevated β-hCG + molar US → gestational trophoblastic disease pathway (uterine evacuation + GTD surveillance) — HG resolves after evacuation. (c) Persistent ketosis + electrolyte derangement despite rehydration → escalate antiemetic ladder + reassess corticosteroid eligibility (refractory + > 10 wk). (d) Unable to maintain nutrition despite optimised antiemetics → nutrition escalation (enteral tube feeding → PPN/TPN last resort). Persistent atypical features → broaden infective/metabolic workup (FUO/occult-source tier if febrile and undifferentiated).
   inputs: tsh_and_free_t4, beta_hcg_quantitative, lfts_and_lipase
   actions: workup.preeclampsia, workup.fuo
   advance: Mimic excluded or routed; HG sub-phenotype branch (uncomplicated / Wernicke-risk / electrolyte-derangement / refractory) selected
7. 7DIFFERENTIAL
   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.
   advance: Mimics excluded or co-managed/routed; HG anchored as clinical diagnosis of exclusion
8. 8RISK_STRATIFICATION
   PUQE score (≤ 6 mild / 7-12 moderate / ≥ 13 severe; Koren PMID 16100620) is the pretest severity instrument; combined with weight-loss %, ketonuria, electrolyte derangement, Wernicke features, and oral-intolerance to set disposition: severe (PUQE ≥ 13 OR Wernicke OR severe electrolyte derangement OR persistent intractable vomiting with ≥ 5 % loss and ketonuria) → admission/IV pathway; moderate (PUQE 7-12, mild dehydration, tolerating some oral) → ambulatory day-case rehydration + ladder escalation (RCOG GTG 69 2024); mild (PUQE ≤ 6) → outpatient first-line antiemetics. qSOFA/SIRS screen if febrile/undifferentiated to detect an infective driver/thyroid storm.
   inputs: duration_and_frequency_of_vomiting, oral_intake_tolerance, maternal_hr
   actions: calc.qsofa, calc.sirs
   advance: Severity tier set; admission-vs-day-case-vs-outpatient decision documented with PUQE basis
9. 9TREATMENT
   ANTIEMETIC LADDER (ACOG PB 189 / RCOG GTG 69 2024 / SOGC): pyridoxine (vitamin B6) 10-25 mg PO q6-8h ± doxylamine 12.5 mg PO first-line → add dimenhydrinate 25-50 mg PO/PR q4-6h OR promethazine 12.5-25 mg PO/PR/IV q4-6h → metoclopramide 5-10 mg PO/IV q6-8h OR ondansetron 4-8 mg PO/IV q8h (counsel limited first-trimester data — small/absent absolute teratogenic risk per Pasternak NEJM 2013 PMID 23488728 + Huybrechts JAMA 2018 PMID 30561479; ECG/QTc caution, avoid high IV doses) → chlorpromazine 10-25 mg PO/IV q4-6h; methylprednisolone 16 mg PO/IV q8h × 3 d then taper RESERVED for refractory disease > 10 wk gestation (Boelig Cochrane PMID 27091683; avoid < 10 wk — oral-cleft signal). REHYDRATION + ELECTROLYTES: IV isotonic crystalloid (NS or LR) to restore volume + clear ketones; KCl replacement guided by serum K+ with cardiac monitoring for severe hypokalemia; correct hyponatremia CAUTIOUSLY (avoid osmotic demyelination). THIAMINE / WERNICKE PROPHYLAXIS: give IV/IM thiamine BEFORE any dextrose-containing fluid or parenteral nutrition; treatment-dose IV thiamine if Wernicke features (Chiossi 2006 PMID 16735862; RCOG GTG 69 2024). NUTRITION ESCALATION: trial enteral (NG/NJ) tube feeding if unable to maintain nutrition on optimised antiemetics; PPN/TPN is a last resort (line sepsis + thrombosis). VTE PROPHYLAXIS (LMWH) if admitted / immobile / dehydrated. Avoid antithyroid drugs for gestational transient thyrotoxicosis (supportive only).
   inputs: current_antiemetic_and_qtc_risk_meds, serum_electrolytes_bmp, gestational_age_weeks
   advance: Antiemetic rung selected, IV rehydration + electrolyte correction started, thiamine given BEFORE any dextrose, nutrition-escalation + VTE-prophylaxis plan documented
10. 10DISPOSITION
    Admission for severe HG (PUQE ≥ 13, Wernicke features, severe electrolyte derangement, persistent intractable vomiting with ≥ 5 % loss + ketonuria, or failed day-case rehydration). Ambulatory day-case IV rehydration + ladder escalation for moderate disease tolerating some oral intake (RCOG GTG 69 2024). Outpatient first-line antiemetics + dietary measures for mild NVP. Critical care for Wernicke encephalopathy with neurologic compromise, thyroid storm, or hemodynamic instability. Early obstetric + dietitian involvement; mental-health support given the high burden + decisional-regret risk. GTD route if molar.
    inputs: gestational_age_weeks, oral_intake_tolerance
    advance: Level of care set (outpatient / day-case / admission / critical care); dietitian + mental-health + OB involvement arranged as indicated
11. 11MONITORING
    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.
    inputs: maternal_weight_trend, serum_electrolytes_bmp, urine_ketones_and_specific_gravity
    actions: panel.cbc, panel.renal
    advance: Vomiting controlled + tolerating oral intake + ketones cleared + electrolytes corrected + weight stabilising
12. 12FOLLOWUP
    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.
    advance: Symptoms controlled on outpatient regimen; weight recovering; mental-health + recurrence + nutrition counseling delivered