---

---

Fever: Differential Diagnosis Approach

Definition

---

Step 1 - Initial Triage: Stable vs. Unstable

• Altered mental status
• Respiratory distress
• Hemodynamic instability (tachycardia, hypotension)

---

Step 2 - Approach to the Stable Febrile Patient

• Positive localizing findings on H&P - Order targeted diagnostic tests; treat/refer accordingly.
• No localizing findings - Screen with UA, CBC, CXR.
  • Positive results - targeted workup/treatment.
  • Negative results - reassess clinical status:
    • Improved - Watchful waiting, symptomatic care.
    • Unchanged - Assign to most likely diagnostic category (Infectious / Autoimmune / Malignancy / Miscellaneous). Consider ANA, RF, ESR for autoimmune; blood/urine cultures; CT for occult infection.
    • Worsened - Additional diagnostics (LP, CT abdomen/pelvis, blood cultures) + empirical broad-spectrum coverage.

---

Step 3 - Differential Diagnosis Categories

A. Infectious Causes (most common treatable causes)

B. Noninfectious Causes (Box 8.1 - Rosen's EM)

• Acute MI, pulmonary embolism/infarction
• Intracranial hemorrhage, CVA
• Neuroleptic malignant syndrome
• Thyroid storm, acute adrenal insufficiency
• Transfusion reaction, pulmonary edema

• CHF, dehydration, recent seizure
• Sickle cell disease, transplant rejection, pancreatitis, DVT

• Drug fever, malignancy, gout, sarcoidosis, Crohn disease

---

Step 4 - Fever of Unknown Origin (FUO)

---

Key History Clues

---

Lab & Imaging Approach

• Respiratory: sputum culture, PCR panel, procalcitonin
• Meningeal signs: LP (cell count, glucose, protein, culture, PCR)
• GI/abdominal: CT abdomen/pelvis
• Cardiac murmur: Echocardiogram, serial blood cultures
• Prolonged FUO: ANA, RF, ESR, CRP, ferritin (markedly elevated in Still's), SPEP, LDH, HIV, hepatitis serologies, PPD/IGRA, CT chest/abdomen/pelvis, PET scan if malignancy suspected

---

• Rosen's Emergency Medicine: Concepts and Clinical Practice (Table 8.1, Box 8.1, Figs. 8.1-8.2)
• Goldman-Cecil Medicine, Ch. 259 (Diagnosis of fever, inpatient vs. outpatient approach)
• Frameworks for Internal Medicine (FUO categories and clinical reasoning framework)

---

• Phase 0 (0-2 min): Safety, positioning, call for help
• Phase 1 (0-5 min): ABCs, O2, IV access, glucose, labs
• Phase 2 (5-20 min): 1st-line benzodiazepines with doses and route selection
• Phase 3/4 (20-60 min): 2nd-line AEDs (fosphenytoin, levetiracetam, valproate, lacosamide) then refractory SE agents (midazolam infusion, propofol, ketamine, phenobarbital, pentobarbital)

---

Case-Based Seizure Management Walkthrough

---

THE CASE

Mr. Arjun R., 34-year-old male Brought to the Emergency Department by his wife at 10:05 AM Chief complaint (per wife): "He collapsed and started shaking while having breakfast. He hasn't woken up properly."

---

SCENE: ARRIVAL - T = 0 min

• Seizure started approximately 8 minutes ago (so this is already established status epilepticus on arrival)
• No prior history of seizures or epilepsy
• No known drug allergies
• Not on any regular medications
• Had complained of headache for 2 days and appeared feverish last night
• No alcohol or drug use
• No recent travel
• Weight approximately 70 kg

---

STEP 1 - IMMEDIATE TEAM RESPONSE (T = 0-2 min)

• Lateral (recovery) position - right lateral decubitus
• Pad side rails, lower bed
• Suction pooled secretions from oropharynx
• Place on cardiac monitor, pulse oximeter
• Two large-bore IVs inserted (right antecubital + left forearm)
• BP cuff - continuous cycling q5 min

• Seizure started ~8 min ago = already status epilepticus (>5 min threshold crossed)
• Fever + headache for 2 days + new-onset seizure = bacterial meningitis must be on the differential until proven otherwise
• SpO2 89% - immediate O2 required

O2 via non-rebreather mask at 15 L/min - target SpO2 > 94%

---

STEP 2 - FIRST-LINE: BENZODIAZEPINE (T = 2-5 min)

╔══════════════════════════════════════════════════════════╗
║  ORDER 1 - FIRST-LINE BENZODIAZEPINE                     ║
║                                                           ║
║  Lorazepam (Ativan) 0.1 mg/kg IV slow push              ║
║  = 0.1 × 70 kg = 7 mg → give 4 mg IV (max per dose)     ║
║                                                           ║
║  Administer over 2 minutes                               ║
║  If seizure continues at 5 min → REPEAT x1               ║
║  Repeat dose: Lorazepam 4 mg IV                          ║
╚══════════════════════════════════════════════════════════╝

---

STEP 3 - SECOND-LINE AED (T = 10-20 min)

• No cardiac monitoring needed (unlike fosphenytoin/phenytoin)
• Safe in patients with unknown cardiac status
• Can be given rapidly
• No interaction with planned meningitis antibiotics

╔══════════════════════════════════════════════════════════╗
║  ORDER 2 - SECOND-LINE AED                               ║
║                                                           ║
║  Levetiracetam (Keppra) 60 mg/kg IV                     ║
║  = 60 × 70 kg = 4200 mg IV                              ║
║  → Give 4000 mg IV in 100 mL NS over 15 minutes         ║
║                                                           ║
║  Rate: 267 mL/h via infusion pump                        ║
╚══════════════════════════════════════════════════════════╝

╔══════════════════════════════════════════════════════════╗
║  ORDER 3 - EMPIRIC MENINGITIS TREATMENT                  ║
║  (Fever + Headache 2 days + New seizure = HIGH SUSPICION ║
║   Do NOT wait for LP - treat immediately)                ║
║                                                           ║
║  Ceftriaxone 2 g IV q12h - STAT first dose               ║
║  Vancomycin 25 mg/kg IV (= 1750 mg) q8-12h - STAT       ║
║  Dexamethasone 0.15 mg/kg IV q6h x4 days                ║
║    = 10.5 mg → give 10 mg IV (before or with 1st abx)   ║
║  Acyclovir 10 mg/kg IV q8h (= 700 mg) - cover HSV       ║
╚══════════════════════════════════════════════════════════╝

---

STEP 4 - REFRACTORY STATUS EPILEPTICUS (T = 22-30 min)

• Seizure has now lasted >22 minutes total
• Two adequate AED agents failed (lorazepam x2 + levetiracetam)
• SpO2 is falling despite O2 - 88% now
• Patient cannot protect airway
• Continuous EEG monitoring needed

RSI Orders:

╔══════════════════════════════════════════════════════════╗
║  ORDER 4 - RSI (RAPID SEQUENCE INTUBATION)               ║
║                                                           ║
║  Pre-oxygenation: 100% O2 via BVM x3-5 min               ║
║                                                           ║
║  INDUCTION:                                               ║
║  Ketamine 2 mg/kg IV = 140 mg IV push                    ║
║    (chosen: hemodynamically stable, may reduce seizures) ║
║                                                           ║
║  PARALYTIC (SHORT-ACTING ONLY):                          ║
║  Succinylcholine 1.5 mg/kg IV = 105 mg IV push           ║
║    *** SHORT-ACTING - duration 10 min ***                ║
║    *** DO NOT use vecuronium/rocuronium long-acting ***  ║
║    *** Paralysis will MASK ongoing seizure activity ***  ║
║                                                           ║
║  Post-intubation: Continuous EEG monitoring - STAT       ║
║  ETT confirmed by waveform capnography + CXR             ║
╚══════════════════════════════════════════════════════════╝

Why short-acting paralytic only? Long-acting paralytics stop the visible shaking but seizure activity continues silently in the brain (non-convulsive SE). EEG is the only way to detect ongoing seizure after paralysis.

Continuous Infusion for Refractory SE:

╔══════════════════════════════════════════════════════════╗
║  ORDER 5 - REFRACTORY SE INFUSION                        ║
║                                                           ║
║  Midazolam (Versed):                                     ║
║    Loading dose: 0.2 mg/kg IV = 14 mg IV bolus           ║
║    Then infusion: start at 0.05 mg/kg/h = 3.5 mg/h      ║
║    Titrate by 0.05 mg/kg/h q15 min to seizure cessation  ║
║    on EEG (max 2 mg/kg/h)                                ║
║                                                           ║
║  Vasopressor on standby (hypotension anticipated):       ║
║  Norepinephrine 0.05-0.3 mcg/kg/min if MAP < 65 mmHg    ║
╚══════════════════════════════════════════════════════════╝

---

STEP 5 - DIAGNOSTIC WORKUP (now seizure is controlled)

╔══════════════════════════════════════════════════════════╗
║  ORDER 6 - STAT LABS & IMAGING                           ║
║                                                           ║
║  Blood:                                                   ║
║  - CBC with differential                                 ║
║  - CMP: Na, K, Ca, Mg, Cl, CO2, BUN, Creatinine, glucose║
║  - LFTs + ammonia                                        ║
║  - Serum lactate                                         ║
║  - Blood cultures x2 (BEFORE antibiotics if possible,   ║
║     but DO NOT delay antibiotics for cultures)           ║
║  - HIV screen                                            ║
║  - CRP, ESR, procalcitonin                               ║
║  - ABG (patient intubated)                               ║
║                                                           ║
║  Imaging:                                                 ║
║  - CT brain non-contrast STAT                            ║
║  - CT brain with contrast (after non-contrast)           ║
║                                                           ║
║  Lumbar Puncture:                                        ║
║  - AFTER CT brain clears herniation risk                 ║
║  - CSF: cell count, glucose, protein, Gram stain,       ║
║    culture, HSV PCR, cryptococcal antigen, VDRL          ║
╚══════════════════════════════════════════════════════════╝

---

STEP 6 - RESULTS & DIAGNOSIS

---

STEP 7 - ONGOING MANAGEMENT & ICU ORDERS

╔══════════════════════════════════════════════════════════╗
║  FINAL STANDING ORDERS - NEURO ICU                       ║
║                                                           ║
║  ANTIBIOTIC REGIMEN (continue):                          ║
║  Ceftriaxone 2 g IV q12h x14 days                       ║
║  Vancomycin - dose by pharmacy per levels                ║
║    (target AUC/MIC 400-600)                              ║
║  Dexamethasone 0.15 mg/kg IV q6h x4 days (COMPLETE)     ║
║    (reduces neurologic complications in pneumococcal)    ║
║  Acyclovir - STOP once HSV PCR returns negative          ║
║                                                           ║
║  SEIZURE PROPHYLAXIS / MAINTENANCE:                      ║
║  Levetiracetam 500 mg IV q12h (maintenance dose)         ║
║  Continue until seizure-free x48h then reassess          ║
║                                                           ║
║  MIDAZOLAM WEAN:                                         ║
║  When EEG seizure-free x24h: decrease by 25% q4-6h      ║
║                                                           ║
║  HYPONATREMIA CORRECTION (Na 128):                       ║
║  Fluid restrict to 1000 mL/24h                          ║
║  3% NaCl NOT needed (Na not < 120, no herniation)        ║
║  Recheck Na q6h; correct no faster than 8-10 mEq/L/day  ║
║  (rapid correction → osmotic demyelination syndrome)     ║
║                                                           ║
║  VENTILATOR SETTINGS (post-intubation):                  ║
║  Mode: Volume AC  TV: 6 mL/kg IBW (= 420 mL)            ║
║  PEEP: 5 cmH2O  FiO2: 0.4  RR: 14                       ║
║  Target: SpO2 >94%, PaCO2 35-40 mmHg                     ║
║                                                           ║
║  MONITORING:                                             ║
║  Continuous EEG x48h minimum                             ║
║  Neuro checks q1h (pupils, GCS as assessable)           ║
║  ICP monitoring if clinical deterioration               ║
║  HOB elevation 30° (reduce ICP)                          ║
╚══════════════════════════════════════════════════════════╝

---

CASE TIMELINE SUMMARY

T = 0 min    → Patient arrives, actively seizing (~8 min into seizure)
               → O2, monitors, IV access, POC glucose
               → STATUS EPILEPTICUS declared

T = 2 min    → Lorazepam 4 mg IV (1st dose)

T = 7 min    → Lorazepam 4 mg IV (2nd dose)
               → No response → move to 2nd-line

T = 10 min   → Levetiracetam 4000 mg IV started (over 15 min)
               → EMPIRIC MENINGITIS antibiotics started (ceftriaxone,
                  vancomycin, dexamethasone, acyclovir)

T = 22 min   → Levetiracetam complete, seizure CONTINUES
               → REFRACTORY SE declared → intubation decision

T = 25 min   → RSI: Ketamine 140 mg IV + Succinylcholine 105 mg IV
               → Intubated; continuous EEG attached

T = 28 min   → Midazolam 14 mg IV bolus + infusion started 0.05 mg/kg/h

T = 35 min   → EEG confirms SEIZURE CESSATION
               → Midazolam titrated to 0.1 mg/kg/h

T = 45 min   → CT brain: meningeal enhancement, no herniation

T = 60 min   → LP performed: CSF confirms bacterial meningitis

T = 90 min   → Patient in Neuro-ICU, sedated but hemodynamically stable
               → Blood cultures growing Gram-positive diplococci
               → Antibiotics narrowed to high-dose ceftriaxone

Day 3        → EEG seizure-free; midazolam weaned and discontinued
               → Extubated; following commands
               → Na corrected to 136 mEq/L

Day 7        → Transfer to step-down; levetiracetam continued orally
               → Neurology follow-up arranged
               → Outpatient EEG in 4 weeks

---

KEY TEACHING POINTS FROM THIS CASE

---

---

Pregnancy-Safe Drugs: Complete Clinical Reference

Understanding Drug Safety in Pregnancy

Golden Rule: Untreated maternal disease is often MORE dangerous to the fetus than treating it with a relatively safe drug.

---

SECTION 1: ANTIBIOTICS IN PREGNANCY

Safe (Preferred):

Use with Caution / Conditional:

CONTRAINDICATED:

---

📋 CASE 1: UTI in Pregnancy

Patient: Priya, 26-year-old, 18 weeks pregnant. Dysuria, frequency, urgency x2 days. Urine dipstick: nitrites +, leukocyte esterase +, no fever.

Cephalexin (Keflex) 500 mg PO QID x 7 days
   (cephalosporins - Category B, safe all trimesters)
OR
Nitrofurantoin (Macrobid) 100 mg ER PO BID x 5 days
   (Category B - safe T1 and T2; AVOID if > 36 weeks)

• Ciprofloxacin (fluoroquinolone - avoid)
• TMP-SMX in T1 (folate antagonist, NTD risk) or T3 (neonatal jaundice)

• All pregnant women should be screened for asymptomatic bacteriuria at first prenatal visit - UTI in pregnancy is a serious condition that can ascend to pyelonephritis
• Treat even asymptomatic bacteriuria in pregnancy (unlike non-pregnant adults)
• Repeat urine culture 7 days after treatment to confirm cure
• Consider suppressive prophylaxis (nitrofurantoin 50-100 mg at bedtime) if recurrent UTIs

---

SECTION 2: ANTIHYPERTENSIVES IN PREGNANCY

Safe (First-Line):

ABSOLUTELY CONTRAINDICATED:

• Chronic HTN: target 140-150/90-100 mmHg (not too tight - avoid uteroplacental insufficiency)
• Severe HTN (≥160/110 mmHg): treat urgently - risk of maternal stroke/eclampsia

---

📋 CASE 2: Hypertensive Emergency in Pregnancy

Patient: Sunita, 32-year-old, 34 weeks pregnant. BP 178/114 mmHg on 2 readings 15 min apart. Severe headache, epigastric pain. Urine protein +++. Platelet count 88,000. LFTs elevated 2x normal.

1. Labetalol 20 mg IV push over 2 min
   If BP still ≥160/110 after 10 min → Labetalol 40 mg IV
   If still not controlled → Hydralazine 5-10 mg IV q20 min
   OR
   Nifedipine 10-20 mg PO, may repeat in 30 min
   TARGET: BP 140-150/90-100 mmHg

2. MAGNESIUM SULFATE - seizure prophylaxis:
   MgSO4 4-6 g IV over 20 min (loading dose)
   Then 1-2 g/h IV continuous infusion
   Monitor: respiratory rate, urine output, reflexes, Mg levels

3. Delivery planning: definitive treatment for HELLP is delivery
   Dexamethasone 12 mg IM q12h x2 doses (fetal lung maturity if <34 wk)

• Magnesium sulfate is NOT an antihypertensive - it is specifically for seizure prevention in preeclampsia
• Toxicity signs of Mg: loss of DTRs (first sign), respiratory depression, cardiac arrest
• Antidote for Mg toxicity: Calcium gluconate 1 g IV push
• NEVER use ACEi or ARB - even a single dose in T2/T3 can cause fetal renal failure

---

SECTION 3: ANALGESICS & ANTIPYRETICS

CONTRAINDICATED:

---

📋 CASE 3: Acute Pain in Pregnancy (Headache/Back Pain)

Patient: Asha, 28-year-old, 24 weeks pregnant. Severe tension headache and low back pain.

1. Paracetamol 500-1000 mg PO q6-8h PRN (max 4 g/day) - FIRST LINE
2. Warm compress for back pain (not hot - no heating pads directly on abdomen)
3. Non-pharmacologic: physiotherapy, support belt for back pain

• Ibuprofen/diclofenac at 24 weeks - although T2 is technically the grey zone, NSAIDs are generally avoided as a habit-forming risk
• Aspirin >150 mg - antiplatelet risk

---

SECTION 4: ANTIEMETICS (Nausea/Vomiting in Pregnancy)

1. Dietary changes + ginger
2. Pyridoxine alone 25 mg TID
3. Add doxylamine (Doxylamine/Pyridoxine combination)
4. Add metoclopramide or promethazine
5. Ondansetron for refractory cases
6. IV fluids + IV antiemetics (admit for hyperemesis gravidarum)

---

📋 CASE 4: Hyperemesis Gravidarum

Patient: Riya, 10 weeks pregnant, 5 kg weight loss, unable to tolerate any oral intake, ketonuria ++, vomiting 12x/day.

ADMIT - IV Access

1. IV Fluids: Normal saline 0.9% + 40 mEq KCl/L @ 125 mL/h
   (correct dehydration + electrolytes)

2. Thiamine 100 mg IV BEFORE glucose infusion
   (prevent Wernicke's encephalopathy)

3. Ondansetron 4 mg IV q8h
   + Metoclopramide 10 mg IV TID

4. Pyridoxine 25 mg IV/PO TID (continue throughout)

5. Once tolerating oral fluids:
   Step down to oral antiemetics
   Doxylamine/Pyridoxine 2 tabs HS

6. Monitor: electrolytes, LFTs (exclude acute fatty liver), TFTs
   (HCG stimulates TSH-R → gestational thyrotoxicosis in 60% of HG)

• Always give thiamine BEFORE IV dextrose to prevent Wernicke's encephalopathy
• Check TFTs: TSH is often suppressed in hyperemesis - transient gestational thyrotoxicosis does NOT need antithyroid treatment, it resolves as HCG falls
• Ondansetron: Use cautiously in T1 (some data for cleft palate), but risk of dehydration from untreated HG outweighs this theoretical risk

---

SECTION 5: ANTIEPILEPTIC DRUGS (AEDs) IN PREGNANCY

• NEVER stop AEDs abruptly (risk of GTCS is more dangerous than AED exposure)
• Use monotherapy at lowest effective dose - polytherapy multiplies risk
• Folic acid 5 mg/day (high-dose) from pre-conception through T1
• Monitor drug levels every trimester (clearance increases in pregnancy)
• Neonates exposed to AEDs - give Vitamin K 1 mg IM at birth (AEDs reduce Vitamin K-dependent clotting factors)

---

SECTION 6: THYROID DRUGS IN PREGNANCY

• T1: Use PTU (less teratogenic in organogenesis period)
• T2 onwards: Switch to Methimazole (PTU has more hepatotoxicity with prolonged use)
• At delivery: Risk of neonatal thyroid disease from maternal antibodies - check neonatal TSH

---

📋 CASE 5: Hyperthyroidism in Pregnancy

Patient: Nidhi, 8 weeks pregnant. Palpitations, tremor, weight loss despite increased appetite. TSH < 0.01, FT4 elevated 3x normal. Anti-TPO antibodies positive. Thyroid scan shows diffuse uptake.

Propylthiouracil (PTU) 100 mg PO TID
   (preferred in T1 - less teratogenic during organogenesis)

Target: FT4 in upper normal range; 
   do NOT normalize TFTs (risk of fetal hypothyroidism)

At 13 weeks: Switch to Methimazole 10-20 mg PO OD

Monitor: TFTs q4 weeks; adjust dose to maintain FT4 high-normal

Check fetal heart rate at each visit - fetal tachycardia suggests 
   fetal hyperthyroidism from maternal antibody transfer

NEVER use: Radioiodine (I-131) - destroys fetal thyroid
NEVER use: Atenolol for prolonged rate control (IUGR risk)
Propranolol: short-term use acceptable for symptomatic tachycardia

---

SECTION 7: ANTICOAGULANTS IN PREGNANCY

---

SECTION 8: ANTIDEPRESSANTS & PSYCHIATRIC DRUGS

1. Review necessity of all drugs
2. Aim for monotherapy at lowest effective dose
3. Restart abruptly-discontinued medication if relapse occurs - relapse is more dangerous
4. Continue throughout pregnancy if condition is severe (depression increases obstetric risk)

---

SECTION 9: ASTHMA DRUGS IN PREGNANCY

---

SECTION 10: ANTIFUNGALS

---

MASTER QUICK-REFERENCE TABLE

---

UNIVERSAL CLINICAL PEARLS FOR PRESCRIBING IN PREGNANCY

1. "The disease treats the fetus too" - untreated hypertension, seizures, asthma, diabetes, and depression all carry significant fetal risk. Never withhold necessary treatment.
2. Folic acid 400 mcg/day for all women planning pregnancy (start 1 month before conception); 5 mg/day for high-risk patients (epilepsy, diabetes, BMI >30, previous NTD).
3. T1 (weeks 1-12) is organogenesis - highest teratogenesis risk. T2/T3 risks are more about fetal growth, function, and neonatal adaptation.
4. Always give the lowest effective dose and for the shortest needed duration.
5. Monotherapy over polypharmacy - drug combinations multiply teratogenic risk non-linearly.
6. Check every drug before prescribing - use TERIS, LactMed, or Drugs@FDA as reference databases.
7. Neonatal effects to watch: Neonatal abstinence syndrome (opioids, benzodiazepines, SSRIs), neonatal hypoglycemia (sulfonylureas, beta-blockers), neonatal bradycardia (labetalol, atenolol), neonatal hypothyroidism (antithyroid drugs).
8. Inform the patient - shared decision-making is essential for all drug prescribing in pregnancy.
9. The 1-month rule: Warfarin embryopathy occurs at weeks 6-12 - risk window overlaps with time before many women know they are pregnant. Women of childbearing age on warfarin MUST use contraception.
10. Supplementation always needed: Iron (from 12 weeks or earlier if anaemic), folic acid, iodine (in iodine-deficient regions), Vitamin D 400-1000 IU/day.

---

---

What's Covered:

OPD Cases (3)

1. Acute Gout - Colchicine, NSAIDs, intra-articular steroid; urate-lowering therapy timing rules
2. OA Knee - Step-up analgesic ladder from paracetamol → topical NSAID → oral COX-2 → IA injection → tramadol
3. Ankle Sprain - POLICE protocol, Ottawa rules, ibuprofen dosing, grading-based management

Ward Cases (3)

1. Post-THR Day 1 - Complete multimodal analgesic regimen, 35-day enoxaparin VTE prophylaxis, hip precautions, bowel care, bone health, physio
2. Open Tibial Fracture Grade IIIB - Emergency resuscitation, Gustilo-graded antibiotic selection with timing, tetanus prophylaxis, fasciotomy monitoring
3. Septic Arthritis - Gram stain-guided empiric antibiotics (vancomycin + ceftriaxone), mandatory drainage, duration by joint type, de-escalation strategy

ICU Cases (3)

1. Acute Compartment Syndrome - Fasciotomy threshold (delta pressure < 30 mmHg), rhabdomyolysis IV fluid protocol, CK monitoring targets
2. Fat Embolism Syndrome - Gurd criteria, methylprednisolone 1.5 mg/kg q8h x3 days, ARDS ventilation principles
3. Diabetic Foot Osteomyelitis + Septic Shock - Sepsis bundle, polymicrobial broad-spectrum empiric (Vancomycin + Pip-Taz), 6-week duration, oral step-down options, glycaemic control