01Approach to the Critical Patient/attcp63

Immediate priorities

›Airway and respiratory threats

›Impending respiratory failure indicators

›Forced vital capacity < 15 mL/kg

›Negative inspiratory force worse than -20 cmH2O

›Paradoxical breathing pattern

›Bulbar dysfunction signs

›Inability to swallow or handle secretions

›Weak cough or pooling of secretions

›Dysphonia progressing to aphonia

›If any respiratory compromise, proceed to early intubation

›Do not delay for lab confirmation

›Aspiration risk is high with bulbar weakness

›Circulation and cardiac threats

›Autonomic dysfunction

›Tachycardia from BoNT autonomic blockade

›Orthostatic hypotension

›Cardiac arrest risk documented in case series

›Continuous cardiac monitoring mandatory

›Sinus tachycardia most common

›Bradycardia and ventricular arrhythmias reported

›If hemodynamic instability, aggressive supportive care

›IV fluid resuscitation for orthostatic hypotension

›Vasopressors if refractory hypotension

Antitoxin and public health activation

›CDC and state health department contact

›24/7 CDC Emergency Operations Center: 770-488-7100

›Required to release Botulism Antitoxin Heptavalent (BAT)

02History/hx57

Presentation pattern

›Classic syndrome

›GI prodrome followed by neurologic decline

›Nausea, vomiting, diarrhea or constipation onset 6 hours to 10 days after ingestion

›Typical onset 12 to 36 hours after exposure

›Cranial nerve involvement beginning

›Diplopia and blurred vision

›Ptosis, dysarthria, dysphonia, dysphagia (the 4 D's)

›Descending paralysis progression

›Cranial nerves to upper extremities to trunk to lower extremities

›Respiratory muscles affected last

Key historical elements

›Food exposure history

›Home-canned vegetables within preceding 12 to 36 hours

›Low-acid vegetables most common: green beans, corn, beets, asparagus

›Duration of storage may span months to years

›Fermented, smoked, or salted meats and fish

›Alaska Native communities: fermented fish type E

›Homemade condiments and sauces stored at room temperature

›Other high-risk vehicles

›Vacuum-packaged commercial products

›Pruno (prison wine) recognized emerging vehicle

Associated symptoms

›Neurologic and autonomic features

›Fatigue and generalized weakness

›Descending pattern essential to recognize

›Symmetric presentation is hallmark

›Autonomic dysfunction

03Physical Exam/exam79

Vital signs and general appearance

›Vital sign pattern

›Temperature

›Afebrile in uncomplicated botulism

›Fever suggests aspiration pneumonia complication

›Respiratory rate

›Tachypnea indicates early respiratory muscle involvement

›Rising rate is ominous sign requiring urgent reassessment

›Heart rate

›Tachycardia from autonomic dysfunction

›Bradycardia possible and dangerous

›Blood pressure

›Orthostatic hypotension from autonomic blockade

›Lying and standing measurements

›General appearance

›Alert and oriented despite profound weakness

›Clear sensorium is hallmark feature

›Confusion suggests alternative diagnosis

›Respiratory effort

›Accessory muscle recruitment

›Paradoxical abdominal movement

Cranial nerve exam

›Ocular findings

›Ptosis

›Bilateral and symmetric

›Distinguishes from unilateral third nerve palsy

›Extraocular movement limitation

›Internal and external ophthalmoplegia

04Differential Diagnosis/ddx42

Life-threatening mimics

›Neurologic emergencies

›Guillain-Barre syndrome

›ICD-10 G61.0

›Ascending paralysis, sensory deficits, elevated CSF protein

›Miller-Fisher variant: descending pattern with ataxia and areflexia

›Brainstem stroke

›ICD-10 I63.9

›Asymmetric findings, altered consciousness, abnormal neuroimaging

›Acute onset distinguishes from gradual botulism

›Myasthenia gravis crisis

›ICD-10 G70.01

›Fatigable weakness, positive edrophonium test, anti-AChR antibodies

›Fluctuating course, sensory and autonomic functions spared

Toxic and infectious mimics

›Toxin-mediated conditions

›Organophosphate poisoning

›ICD-10 T60.0

›Miosis not mydriasis, SLUDGE syndrome (excessive secretions)

›Cholinergic crisis with bradycardia and bronchospasm

›Tick paralysis

›ICD-10 T63.4

›Ascending paralysis, full recovery after tick removal

›Search for embedded tick in hairline and skin folds

›Shellfish and tetrodotoxin poisoning

›Paresthesias prominent, rapid onset within minutes to hours

›No muscarinic autonomic features

›Infectious conditions

05Laboratory Tests/lt57

Toxin detection

›Serum botulinum toxin assay

›Mouse bioassay

›Gold standard for toxin detection

›Results require 1 to 4 days

›Send to state public health laboratory or CDC

›Endopeptidase mass spectrometry (Endopep-MS)

›Faster alternative to mouse bioassay

›Available at CDC and select reference laboratories

›Detection window up to 12 days post-ingestion in serum

›Urine toxin detection

›May extend detection window to 25 days

›Emerging assay methodology

Stool and culture testing

›Stool specimens

›Stool toxin detection

›Highest yield specimen type in foodborne botulism

›Collect before cathartic or enema use

›Stool culture for C. botulinum

›Low yield but provides serotype confirmation

›Anaerobic culture required

›Gastric contents and vomitus

›Submit if available, especially early presentation

›Do not discard suspect food material

Routine laboratory studies

›Standard chemistry panel

›Complete blood count

›Typically normal in uncomplicated botulism

06Diagnostic Tests/dt62

Scoring Systems

›Botulism severity assessment

›No validated scoring system specific to botulism

›Clinical acuity determined by respiratory and bulbar function

›Serial FVC and NIF are functional severity markers

›Severity classification by clinical phenotype

›Mild: cranial nerve palsies only, no respiratory compromise

›Moderate: limb weakness, FVC > 15 mL/kg

›Severe: respiratory failure, FVC < 15 mL/kg, intubation required

›Sequential Organ Failure Assessment (SOFA) for ICU patients

›Tracks multiorgan dysfunction during prolonged course

›Not botulism-specific but useful for ICU prognostication

MRI

›MRI brain

›Typical findings in botulism

›Normal in 82% of patients on neuroimaging

›Obtained primarily to exclude brainstem stroke

›Indications

›Asymmetric neurologic findings

›Altered mental status suggesting structural cause

›Protocol

›DWI sequences for acute stroke exclusion

›FLAIR for inflammatory or demyelinating lesions

›MRI spine

›Indications

›Atypical weakness pattern

›Cauda equina enhancement reported in adult intestinal toxemia variant

›Limitations

07Disposition/dispo39

Admission criteria

›All suspected cases require hospital admission

›No safe outpatient observation threshold for botulism

›Respiratory failure can develop rapidly and unpredictably

›Clinical diagnosis alone is sufficient to admit

›ICU indications

›Any bulbar weakness

›Any respiratory symptoms or FVC decline

›Need for antitoxin administration

›Rapidly progressive descending weakness

Transfer criteria

›Interfacility transfer indications

›Transfer to facility capable of prolonged mechanical ventilation

›Weeks to months of ventilator support may be required

›Critical care and neurology expertise required

›Antitoxin access

›CDC and state health department coordinate BAT release

›Antitoxin may be transported to receiving facility

›Transfer timing

›After airway secured and patient stabilized

›Do not delay antitoxin for transfer logistics

Public health disposition

›Mandatory reporting obligations

›State health department notification within 24 hours

›Botulism is a Category A bioterrorism agent

›Outbreak investigation triggers food recall

›CDC coordination

›BAT release coordination

08Treatment/t102

Antitoxin therapy

›Botulism Antitoxin Heptavalent (BAT)

›Agent details

›Equine-derived F(ab')2 fragments covering serotypes A through G

›Licensed in the United States 2013

›Held in Strategic National Stockpile

›Dosing

›One vial IV in adults and children over 1 year

›Dilute in normal saline prior to infusion

›Infuse over 30 to 60 minutes with rate titration

›Efficacy

›Reduces mortality OR 0.16 (95% CI 0.09 to 0.30)

›Predicted survival > 95.9% with treatment

›Early administration (within 2 days of onset) reduces ICU stay from 12 to 4 days

›Early administration reduces ventilation duration from 14.5 to 6 days

›Timing

›Administer immediately upon clinical suspicion

›Do not wait for laboratory confirmation

›Antitoxin neutralizes only unbound toxin

Antitoxin hypersensitivity management

›Pre-treatment preparation

›Hypersensitivity risk assessment

›Equine-derived product: anaphylaxis in approximately 2%

›Serum sickness in approximately 4%

›Prior equine serum exposure increases risk

›Skin testing

›Perform intradermal skin test prior to infusion per manufacturer protocol

›Diluted product in forearm

›Premedication

›Diphenhydramine 25 to 50 mg IV or IM prior to infusion

›Methylprednisolone 125 mg IV for high-risk patients

›Emergency preparation

›Epinephrine 1:1000 0.3 mg IM at bedside

›Resuscitation equipment immediately available

Airway and ventilation management

›Intubation strategy

›Intubation triggers

›FVC < 15 mL/kg

›NIF worse than -20 cmH2O

›Clinical deterioration or bulbar failure

›Technique

›Rapid sequence intubation

›Avoid succinylcholine if prolonged denervation anticipated

›Rocuronium 1.2 mg/kg IV for RSI

›Post-intubation

›Lung protective ventilation strategy

›Tidal volume 6 to 8 mL/kg ideal body weight

›PEEP 5 to 8 cmH2O initial setting

›Prolonged ventilation planning

›Tracheostomy consideration

›If mechanical ventilation anticipated > 14 days

›Facilitates weaning and secretion management

›Ventilator weaning criteria

›FVC recovering above 15 mL/kg

›NIF improving beyond -25 cmH2O

›Synchrony with ventilator trials

Drugs to avoid

›Contraindicated and dangerous medications

›Aminoglycosides

›Gentamicin, tobramycin, amikacin

›Potentiate neuromuscular blockade

›Use alternative antibiotics if aspiration pneumonia treated

›Magnesium sulfate

›Potentiates presynaptic NMJ blockade

›Avoid even for tocolysis in pregnancy

›Neuromuscular blocking agents

›Potentiated effect with botulism toxin present

›Use only if absolutely required for intubation with lowest effective dose

›Clindamycin

›May worsen NMJ blockade at high doses

›Use with caution if required for anaerobic coverage

GI decontamination

›Decontamination strategy

›Consider if ingestion recent and ileus absent

›Whole bowel irrigation to clear residual toxin

›Activated charcoal if very early presentation (< 1 to 2 hours)

›Avoid magnesium-containing cathartics

›Potentiates neuromuscular blockade

›Use polyethylene glycol-based solutions instead

›Enemas

›Non-magnesium based enemas acceptable for constipation

›Fleet phosphate enema or saline enema

Supportive care

›Nutritional support

›NPO if dysphagia present

›Aspiration risk with any bulbar dysfunction

›Early gastric or post-pyloric feeding tube placement

›Enteral nutrition preferred

›Target 25 to 30 kcal/kg/day

›Protein 1.2 to 2 g/kg/day during acute illness

›Parenteral nutrition

›If enteral route not tolerated

›Avoid over-feeding

›Thromboembolic prophylaxis

›Pharmacologic prophylaxis

›Enoxaparin 40 mg subcutaneous daily

›Initiate once hemorrhagic risk acceptable

›Mechanical prophylaxis

›Sequential compression devices

›Initiated immediately on admission

›Eye care

›Corneal protection

›Lubricating eye drops hourly if unable to blink

›Moisture chamber or taping for exposure keratopathy prevention

›Physical and occupational therapy

›Early passive range of motion

›Prevent contractures during prolonged immobility

›Daily assessment of functional recovery

09Special Populations/sp62

Pregnancy

›Physiologic considerations in pregnancy

›Botulinum toxin does not cross placenta

›Maternal disease does not directly harm fetus via toxin

›Maternal hypoxia is the primary fetal risk

›Respiratory compromise risk

›Elevated diaphragm reduces functional residual capacity

›Lower threshold to intubate in third trimester

›PaO2 targets > 70 mmHg to maintain fetal oxygenation

›Treatment modifications in pregnancy

›BAT antitoxin safety

›Equine-derived product: use if clinical benefit outweighs risk

›No adequate human studies on fetal effects

›Life-threatening maternal illness justifies use

›Drug avoidance

›Magnesium sulfate contraindicated even for obstetric indications

›Aminoglycosides avoid if possible due to combined fetal and NMJ risks

›Fetal monitoring

›Continuous electronic fetal monitoring during acute illness

›Obstetrics consultation immediately

›Delivery considerations

›Premature labor may occur with severe maternal illness

›Neonatal intensive care team on standby

Geriatric

›Age-specific risks

›Reduced respiratory reserve

›Earlier intubation threshold in elderly

›Baseline FVC lower with aging

10Background/b62

Epidemiology

›Disease burden in the United States

›Incidence

›Approximately 24 cases of foodborne botulism reported annually in the US

›Rare disease but mortality disproportionate if untreated

›Mortality

›Historical mortality 40 to 50% without treatment

›Modern mortality < 10% with antitoxin and ICU support

›Geographic distribution

›Alaska: highest per capita incidence from fermented traditional foods

›Nationwide: home canning events most common vehicle

›Serotype distribution

›Types A and B

›Most common in US foodborne cases

›Type A causes more severe and prolonged illness

›Type E

›Associated with fish and marine products

›Alaska Native communities predominantly affected

›Types C through G

›Rare in human foodborne illness

›BAT covers all seven serotypes A through G

Pathophysiology

›Toxin mechanism

›Botulinum neurotoxin (BoNT) structure

›150 kDa zinc-dependent endopeptidase

›Heavy chain mediates neurospecific binding and endocytosis

›Light chain cleaves SNARE proteins

›SNARE protein targets by serotype

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Discharge instructions for Botulism (Foodborne)

›What happened

›You were diagnosed with foodborne botulism, a serious illness caused by a toxin produced by the bacterium Clostridium botulinum in improperly preserved food

›You received antitoxin treatment and supportive care to help your body recover

›Recovery expectations

›Recovery from botulism is slow and may take weeks to months

›Weakness, fatigue, and difficulty with vision or swallowing may persist after discharge

›Nerve endings must regrow, which takes time

›Medications and follow-up

›Take all prescribed medications as directed

›Attend all scheduled follow-up appointments with neurology

›Physical and occupational therapy referrals may help regain function

›Food safety instructions

›Do not consume any remaining food from the implicated batch

›Discard any similarly prepared home-canned or preserved foods

›Home-canned foods should be boiled for at least 10 minutes before eating

›Use proper pressure canning techniques for low-acid vegetables

›Refrigerate all preserved foods and discard bulging or damaged cans

›Botulism toxin is odorless and tasteless in contaminated food

›Swallowing and diet precautions

›Follow recommendations of speech-language pathology regarding diet texture

›Do not eat solid food if swallowing feels unsafe

›Eat in an upright position

›Return to emergency department immediately for

›New or worsening difficulty breathing or shortness of breath

›Worsening weakness in arms or legs

›New difficulty swallowing or handling secretions

12References/r37

Guidelines and key sources

›Shapiro RL, Hatheway C, Swerdlow DL

›Botulism in the United States: A Clinical and Epidemiologic Review

›Annals of Internal Medicine 1998

›PMID 9696731

›Sobel J

›Botulism

›Clinical Infectious Diseases 2005

›PMID 16163636

›Rao AK, Lin NH, Jackson KA et al

›Clinical Characteristics and Ancillary Test Results Among Patients With Botulism, United States 2002 to 2015

›Clinical Infectious Diseases 2017

›PMID 29293936

›Yu PA, Lin NH, Mahon BE et al

›Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin

›Clinical Infectious Diseases 2017

›PMID 29293928

›O'Horo JC, Harper EP, El Rafei A et al

›Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: Systematic Review and Meta-Analysis 1923 to 2016

›Clinical Infectious Diseases 2017

›PMID 29293927

›Chalk CH, Benstead TJ, Pound JD, Keezer MR

›Medical Treatment for Botulism

›Cochrane Database of Systematic Reviews 2019

›Lonati D, Schicchi A, Crevani M et al

›Foodborne Botulism: Clinical Diagnosis and Medical Treatment

›Toxins 2020

›PMID 32784744

Evidence & Review