TopicsThrombolysis · Code blueUpdated November 2026

Anaphylaxis with TNK/tPA

Alteplase (tPA) or tenecteplase (TNK) anaphylaxis: rare, probably under-recognized, and time-critical. This page pairs the SiLab bedside outline with a new section of code blue charts on anaphylactoid vs IgE-mediated anaphylaxis, coding, and toxidromes.

01 / Thrombolysis

Anaphylaxis with alteplase (tPA) or TNK

Incidence and risk
- Incidence unknown but likely underestimated.
- Early data: 4 cases in >1 million doses (very low).
- Recent studies suggest higher: up to 1.9% in stroke patients.
- Medicare study: 8-fold increased risk with IV thrombolysis (OR 7.8).
- Absolute risk still small: 0.54% vs 0.07% without thrombolysis.
- Risk context: anaphylaxis 1 in 200 vs ICH 1 in 16 vs orolingual angioedema 1 in 45.
Clinical presentation
- Can occur after the bolus and/or during the infusion.
- Spectrum from orolingual angioedema (2.2% incidence) to full anaphylaxis.
- Classic signs: urticaria, angioedema, bronchospasm, hypotension.
- Additional: erythema, laryngeal edema, arrhythmias, feeling of doom.
- Rapid onset suggests a more severe reaction.
- Largely a clinical diagnosis.
Mechanisms
- Type 1 (IgE-mediated) hypersensitivity is rare given low antigenicity.
- More likely systemic hypersensitivity from vasoactive mediator release.
- Mast cell / basophil release: histamine, tryptase, leukotrienes.
- ACE-inhibitor interaction increases orolingual angioedema risk — plasmin activates complement → kinins; ACE inhibitors block bradykinin breakdown.
- Anaphylaxis can be prothrombotic and reduce cerebral blood flow.
Diagnosis and monitoring
- Clinical diagnosis is primary.
- Serum tryptase: a rise >2 μg/L has moderate sensitivity and high specificity — best compared with baseline; correlates with severity; useful post-mortem if obtained <15 hours.
- Specific IgE to alteplase is detectable but research-only.
- Guidelines emphasize frequent cardiopulmonary monitoring after thrombolysis.
- Watch for facial angioedema and respiratory distress during the infusion.
Management
- Ask for help. Don’t be shy to call a code blue, STAT ED, or ICU staff consult.
- Minor reaction: stop the infusion immediately to prevent dose-dependent escalation.
- Severe reaction protocol: IV hydrocortisone (200 mg IV push), IV ranitidine (25–50 mg IV push), IM epinephrine (0.3–0.5 mg IM).
- May require intubation and ICU transfer.
- Consider speaking with the blood bank / transfusion medicine specialist on call.
- Consider Berinert ↗ (C1 esterase inhibitor) for refractory cases — plasma-derived C1 esterase inhibitor can be effective when standard treatment fails, is particularly useful given the bradykinin-mediated mechanism, and case reports show resolution of airway compromise and avoidance of invasive airway procedures.
- Risk–benefit analysis before re-challenge after a Type 1 reaction.
Outcomes
- Medicare study: anaphylaxis associated with higher mortality (OR 1.9).
- Case reports describe stroke following anaphylaxis via prothrombotic mechanisms.
- Reduced cerebral blood flow from decreased cardiac output and vasospasm.

02 / Code blue charts

Anaphylactoid vs anaphylaxis in the code blue New

New section. Charts and references summarized from an OpenEvidence search ↗ (a three-question thread: how anaphylactoid and anaphylactic reactions differ at the bedside and during a code blue, how they are coded, and how to recognize toxidromes in a code). Accessed November 2, 2026. The source’s images are not reproduced. This is an AI-assisted evidence summary, not SiLab or institutional guidance — verify doses against the primary references and local protocols.

A · BedsideAnaphylactoid vs IgE-mediated anaphylaxis

At the bedside there is no clinical difference. Recognize and treat anaphylactoid (non-IgE) and IgE-mediated anaphylaxis exactly the same way — and that applies during a code blue too. The two produce indistinguishable signs, have the same severity, and respond to epinephrine in the same way.^[1,2,3] The emergency treatment is identical.^[4] The mechanism only matters afterward, when choosing allergy testing and planning long-term avoidance.^[1,4] Current terminology drops “anaphylactoid” in favour of “anaphylaxis,” which is later subtyped as allergic or non-allergic once testing is done.^[1,5]

Table A1 · What actually differs (and doesn’t)
Feature	IgE-mediated anaphylaxis	Anaphylactoid (non-IgE)	Refs
Mechanism	Allergen cross-links IgE on mast cells and basophils	Direct mast cell activation (e.g., MRGPRX2), complement, or COX-1 shunting	4, 5, 6
Prior sensitization	Required	Not required; can happen on first exposure	2, 3, 4
Typical triggers	Foods, insects, antibiotics, NMBAs, latex	Radiocontrast, NSAIDs, opioids/vancomycin, some induction agents	4, 5
Clinical picture and severity	Can be identical	Can be identical	1, 2, 5
Acute treatment	Epinephrine-based	Same	3, 4
Tryptase	Usually elevated	Elevated to a lesser degree	3
Skin tests / specific IgE	Useful	Of no value; only challenge testing helps	1, 4

Recognition during a code

Suspect it with sudden hypotension, bronchospasm or high airway pressures, angioedema or stridor, or PEA arrest within minutes of a drug, contrast, or blood product — even if the patient has never been exposed before.
Skin signs may be absent when the patient is in shock or under drapes. Perioperative anaphylaxis is often recognized late.^[7]
Draw a serum tryptase during the event, whatever the suspected mechanism. It confirms that mast cells were activated.^[3]

After the event

Document the suspected agent and draw tryptase so the patient can be referred to allergy. If the reaction was non-IgE, a negative skin test or negative specific IgE does not clear the drug. Management is avoidance, or premedication and challenge for agents like contrast, as directed by the allergist.^[1,4]

Management (identical for both)

Stop the trigger right away (infusion, contrast, blood product).^[7]
Peri-arrest shock with an IV in place: epinephrine 0.05–0.1 mg IV (5–10% of the arrest dose). Start an infusion at 5–15 mcg/min if shock recurs. With no IV, give 0.5 mg IM (0.3 mg autoinjector; 0.15 mg pediatric).^[8]
Cardiac arrest: standard ACLS with 1 mg IV/IO epinephrine. Standard IM or autoinjector doses may not be enough once the patient has arrested.^[7,8]
Airway: intubate early if there is edema, and prepare for a surgical airway.^[8]
Aggressive isotonic fluids: up to 73% of infused fluid can leak out of the vessels.^[7]
Refractory shock on a β-blocker: glucagon 1–5 mg IV for adults (20–30 mcg/kg, max 1 mg, for children).^[7]
ECMO/ECPR is reasonable in refractory cases. Sugammadex for rocuronium-associated reactions is supported only by case-level data.^[7]
Antihistamines, inhaled β-agonists, and IV steroids have no proven benefit during the arrest itself.^[8]

B · CodingCoding and documentation

ICD-10-CM codes the two terms the same way. In the Alphabetic Index, “anaphylactoid reaction/shock” points to “Shock, anaphylactic.” Anaphylactoid (non-IgE) and anaphylactic (IgE-mediated) reactions therefore use the same T-codes. The code depends on the trigger, not the mechanism. When the trigger is documented, use the specific code; T78.2 is only for when no cause is known.

Table B1 · Diagnosis codes by trigger (ICD-10-CM)
Scenario	Code	Note
Trigger unknown or not documented	T78.2XXA: anaphylactic shock, unspecified	Default when no cause is identified
Food trigger	T78.0- (e.g., T78.01XA peanuts, T78.02XA shellfish, T78.00XA unspecified food)	Use the food-specific subcode
Drug given correctly (including iodinated contrast, antibiotics, NMBAs, opioid-related histamine release)	T88.6XXA: anaphylactic reaction due to adverse effect of correct drug properly administered	Add the T36–T50 adverse-effect code (6th character 5) for the drug
Drug overdose, wrong drug, or wrong dose	T36–T50 poisoning code (sequenced first) + T78.2XXA	Poisoning rules apply
Serum, blood product, or vaccine	T80.5- series	Choose by agent
Cardiac arrest during the event	I46.8: cardiac arrest due to other underlying condition	Sequence after the anaphylaxis code; use I46.9 only if the cause is undocumented

In the source, T88.6, the T80.5- series, and the T36–T50 adverse-effect codes were not shown in the CMS code tables used. Check the exact characters in the current ICD-10-CM files before submitting.

Procedure and professional codes for the code blue

92950: CPR, billed once per resuscitation.
99291 / 99292: critical care, first 30–74 minutes, then each additional 30 minutes. Time spent on separately billed procedures (CPR, intubation 31500, central line) has to be subtracted from critical care time.

Documentation points

Write “anaphylactoid reaction to [agent],” not just “anaphylactoid reaction.” Without the agent, coders are limited to T78.2XXA, the least specific code.
If the patient had a cardiac arrest, record the arrest, the rhythm, and its link to the reaction (e.g., “cardiac arrest secondary to anaphylactoid reaction to IV contrast”). This supports I46.8 and the right sequencing.

Canadian context

The codes above are US codes (ICD-10-CM diagnoses; CPT procedure and critical-care billing codes), as given in the source. Canadian hospitals code diagnoses with ICD-10-CA and interventions with CCI, and Ontario physician billing uses the OHIP Schedule of Benefits — confirm local equivalents with your health records team. The documentation points apply everywhere.

Editorial note added on ncrit.dev

C · DifferentialToxidromes in the code blue: when it may not be anaphylaxis

A toxidrome is a group of signs that points to a class of poison. During a code, look at five bedside findings: mental status, pupils, skin (wet or dry), heart rate and BP, and temperature/neuromuscular signs. Together these let you pick a likely poison class and give an empiric antidote while resuscitation goes on, without waiting for labs.^[9,10] The classic six are opioid, sympathomimetic, serotonergic, antimuscarinic (anticholinergic), muscarinic, and nicotinic (cholinergic). Others matter in a code: knockdown/asphyxiant, bradycardia with hypotension, NMS, and uncoupling of oxidative phosphorylation.^[10] Toxidromes are probabilistic, not definitive. Mixed or incomplete pictures are common, so failing to see a “textbook” pattern does not exclude poisoning.^[10]

Table C1 · Classic toxidromes: rapid recognition
Toxidrome (examples)	HR/BP	Temp	Pupils	Skin	Mental status / other	Key code action	Refs
Opioid (heroin, fentanyl, morphine)	decreased	decreased	Pinpoint	—	Coma, apnea/hypoventilation	Naloxone; ventilate	7, 10, 11
Sedative-hypnotic (benzodiazepines, EtOH)	decreased	decreased	Normal	—	Coma, respiratory depression	Supportive; flumazenil rarely (many contraindications)	9, 11
Sympathomimetic (cocaine, amphetamines)	increased	increased	Large, reactive	Diaphoretic	Agitation, seizures	Benzodiazepines, rapid cooling; NaHCO₃ for cocaine wide-QRS dysrhythmias	7, 9, 11
Anticholinergic (antihistamines, TCAs, atropine)	increased	increased	Large, sluggish	Dry, flushed	Delirium, hallucinations, urinary retention	Supportive; NaHCO₃ if wide QRS (Na-channel blockade)	9, 11
Cholinergic (organophosphates, carbamates)	decreased	no typical change	Small	Wet/diaphoretic	Bronchorrhea, salivation, emesis, diarrhea, weakness/fasciculations, seizures	High-dose atropine, pralidoxime, early intubation, staff PPE	7, 9, 11
Serotonergic (SSRIs/SNRIs, MAOIs)	increased	increased	Large	Diaphoretic	Clonus, hyperreflexia, agitation	Benzodiazepines, cooling	10

The two that tell you most: pupils and skin

Pinpoint pupils plus apnea suggests opioid. Pinpoint pupils plus wet skin, bronchorrhea, and bradycardia suggests cholinergic.^[9,11]
Mydriasis plus hyperthermia: dry skin suggests anticholinergic; sweaty skin suggests sympathomimetic or serotonergic. Clonus or hyperreflexia points to serotonergic.^[10,11]

Code-relevant toxidromes beyond the classic six

Bradycardia with hypotension: β-blockers, CCBs, digoxin, clonidine, organophosphates. Each needs different treatment, so look for features that tell them apart. Options include calcium, glucagon, high-dose insulin (start early), digoxin Fab, and atropine.^[7,9,10]
Knockdown/asphyxiant (cyanide, CO): sudden collapse, often a fire victim, with CNS depression, bradycardia, and high lactate. Give hydroxocobalamin 5 g empirically without waiting for confirmation.^[7,9]
Local anesthetic toxicity (bupivacaine): seizures or arrest shortly after a block. Give 20% lipid emulsion.^[7,9]
Wide-QRS dysrhythmias (TCAs, cocaine, other Na-channel blockers): standard ACLS plus sodium bicarbonate.^[9]
Methemoglobinemia: cyanosis that does not improve with oxygen. Give methylene blue.^[7]

Practical code workflow

ABCDE resuscitation first, with the toxidrome assessment running alongside it.^[10]
Rapid labs: glucose, electrolytes/anion gap, lactate, blood gas with co-oximetry, and ECG (QRS/QTc). These narrow the differential quickly.^[12]
A timely response to an antidote (e.g., naloxone) strongly supports the diagnosis.^[10]
Start VA-ECMO activation early for refractory toxic shock or dysrhythmias; setup takes time.^[7,9]
Call a poison centre or toxicologist early.^[9] The source lists the US Poison Help line, 1-800-222-1222.

In Canada: call 1-844-POISON-X (1-844-764-7669), which routes to your regional poison centre 24/7 (Québec: 1-800-463-5060). Health Canada ↗

Editorial note added on ncrit.dev

Table C2 · Key antidote doses during a code (adult)
Antidote	Indication	Initial dose	Refs
Naloxone	Opioid	0.2–2 mg IV/IO/IM (2–4 mg IN), repeat q2–3 min; don’t interrupt CPR	7
Atropine	Organophosphate / carbamate	1–2 mg, double q5 min until chest clear, HR >80, SBP >80	7, 9
Pralidoxime	Organophosphate	2 g IV over 15–30 min (no bolus)	7
Calcium chloride	β-blocker / CCB	2 g (20 mL of 10%), central line preferred	7
High-dose insulin	β-blocker / CCB	1 U/kg + dextrose, then 1–10 U/kg/h	7
Glucagon	β-blocker / CCB	2–10 mg (expect vomiting)	7
Hydroxocobalamin	Cyanide	5 g	7
20% lipid emulsion	Local anesthetic	>70 kg: 100 mL over 2–3 min; <70 kg: 1.5 mL/kg	7
Digoxin Fab	Digoxin	10–20 vials if critically ill and dose unknown	7
Methylene blue	MetHb, CCB vasoplegia	1–2 mg/kg (max 7 mg/kg)	7

The source closes by noting that the Nature Reviews Disease Primers framework places toxidrome assessment at the centre of poisoning management — after resuscitation and before targeted therapy.^[10] Its figure is not reproduced here.

ReferencesReferences for the code blue charts

Ewan PW, Dugué P, Mirakian R, et al. BSACI guidelines for the investigation of suspected anaphylaxis during general anaesthesia. Clin Exp Allergy. 2010;40(1):15–31. doi.org/10.1111/j.1365-2222.2009.03404.x
Flick R, Pabelick CM, Harrison TE, et al. Clinical complications in pediatric anesthesia. In: Gregory’s Pediatric Anesthesia. Wiley; 2020. onlinelibrary.wiley.com/doi/10.1002/9781119371533.ch45
Castells MC, Phillips EJ. Maintaining safety with SARS-CoV-2 vaccines. N Engl J Med. 2021;384(7):643–649. doi.org/10.1056/NEJMra2035343
Misbah S, Spickett G, Dalm V. Anaphylaxis and allergy. In: Chapel and Haeney’s Essentials of Clinical Immunology. 7th ed. Wiley; 2023. onlinelibrary.wiley.com/doi/10.1002/9781394321803.ch4
Gaudio FG, Johnson DE, DiLorenzo K, et al. Wilderness Medical Society clinical practice guidelines on anaphylaxis. Wilderness Environ Med. 2022;33(1):75–91. doi.org/10.1016/j.wem.2021.11.009
Ebo DG, Beyens M, Heremans K, et al. Recent knowledge and insights on the mechanisms of immediate hypersensitivity and anaphylaxis: IgE/FcεRI- and non-IgE/FcεRI-dependent anaphylaxis. Curr Pharm Des. 2023;29(3):178–184. doi.org/10.2174/1381612829666221025091827
Cao D, Arens AM, Chow SL, et al. Part 10: Adult and pediatric special circumstances of resuscitation: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2025;152(16_suppl_2):S578–S672. doi.org/10.1161/CIR.0000000000001380
Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult basic and advanced life support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142(16_suppl_2):S366–S468. doi.org/10.1161/CIR.0000000000000916
Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning. Circulation. 2023;148(16):e149–e184. doi.org/10.1161/CIR.0000000000001161
Roberts DM, Nic Ionmhain Ú, Trakulsrichai S, et al. Toxidromes. Nat Rev Dis Primers. 2026;12(1):60. doi.org/10.1038/s41572-026-00736-4
Mangus CW, Canares TL. Toxic ingestions: initial management. Pediatr Rev. 2018;39(4):219–221. doi.org/10.1542/pir.2017-0119
Henretig FM, Kirk MA, McKay CA. Hazardous chemical emergencies and poisonings. N Engl J Med. 2019;380(17):1638–1655. doi.org/10.1056/NEJMra1504690

Anaphylaxis with TNK/tPA

Anaphylaxis with alteplase (tPA) or TNK

Incidence and risk

Clinical presentation

Mechanisms

Diagnosis and monitoring

Management

Outcomes

Anaphylactoid vs anaphylaxis in the code blue New

A · BedsideAnaphylactoid vs IgE-mediated anaphylaxis

Recognition during a code

After the event

Management (identical for both)

B · CodingCoding and documentation

Procedure and professional codes for the code blue

Documentation points

Canadian context

C · DifferentialToxidromes in the code blue: when it may not be anaphylaxis

The two that tell you most: pupils and skin

Code-relevant toxidromes beyond the classic six

Practical code workflow

ReferencesReferences for the code blue charts

Further reading