Pontine Haemorrhage

Epidemiology & Aetiology

• Arterial hypertension (most common) — causes lipohyalinosis and fragility of small penetrating arteries
• Vascular malformations — cavernous malformations (more common in younger patients; tend to be subependymal, more discrete, and do not rupture into the ventricle, but carry a risk of rebleeding)
• Clotting disorders, trauma

Pathophysiology & Anatomy

Clinical Classification

Clinical Features — Classic (Massive) Pontine Haemorrhage

Consciousness

• Coma begins abruptly in the majority; ~50% of patients present in coma

The "Classic Tetrad"

1. Pinpoint (miotic) pupils (2–3 mm), but reactive to light (requires magnifying glass to detect the reaction) — due to bilateral interruption of descending sympathetic fibres with preserved parasympathetic outflow via CN III
2. Absent oculovestibular/oculocephalic responses (horizontal eye movements lost)
3. Quadriplegia (often flaccid acutely, or decerebrate posturing)
4. Irregular/ataxic breathing — Cheyne-Stokes, apneustic, or gasping patterns

Other findings

• Ocular bobbing (or its variants) — rapid downward jerk with slow return
• Hyperthermia (38.5–40°C) within hours, seen in nearly all survivors beyond a few hours — due to involvement of thermoregulatory pathways
• Bradycardia
• If the haemorrhage extends into the midbrain: pupils may become asymmetric or dilate to midposition

Clinical Data (80 patients with pontine haemorrhage)

Less Severe Forms

Diagnosis

• Sudden coma
• Periodic or ataxic breathing
• Pinpoint pupils
• Absent oculovestibular responses
• Quadriplegia

Imaging

Poor Prognostic Features

• Coma on presentation
• Absence of oculocephalic reflexes
• Absent corneal reflexes
• No motor responses
• Hypertension + tachycardia
• Hyperthermia (core ≥39°C)
• Acute obstructive hydrocephalus
• Intraventricular blood extension

Management

• Medical (supportive): Airway protection, blood pressure control, treatment of hyperthermia, management of hydrocephalus (external ventricular drain if obstructive hydrocephalus develops)
• Surgery: Generally has no role in hypertensive brainstem haemorrhages. However, for superficially located cavernous angiomas, surgical evacuation is sometimes appropriate — these have a better prognosis and a tendency to rebleed

Key Differential Diagnoses

Tramadol Poisoning

Pharmacology (Relevant to Toxicity)

1. Weak μ-opioid receptor agonism — via its active metabolite O-desmethyltramadol (M1), produced by CYP2D6. M1 has greater μ-receptor affinity than the parent drug and an elimination half-life of ~9 hours.
2. Serotonin and norepinephrine reuptake inhibition (SNRI-like) — contributes to both analgesia and toxicity

Dose-Related Toxicity

Clinical Features of Tramadol Poisoning

1. Opioid Toxidrome (Partial)

• CNS depression — lethargy → stupor → coma
• Respiratory depression — slow, shallow breathing; hypercarbia, hypoxia, cyanosis
• Miosis — though less consistently than pure opioids
• Nausea, vomiting, ileus, urinary retention

2. Seizures (hallmark feature)

• Common and distinctive — tramadol lowers the seizure threshold
• Usually generalised tonic-clonic, typically single and self-limiting
• Naloxone does not prevent tramadol-induced seizures
• Anticonvulsants (benzodiazepines) are the treatment of choice
• Risk is amplified by co-administration of other seizure-threshold-lowering drugs (antidepressants, antipsychotics, bupropion)

3. Serotonin Syndrome

• In isolated tramadol overdose
• Much more commonly when combined with SSRIs, SNRIs, MAOIs, TCAs, linezolid, dextromethorphan

• Altered mentation (anxiety → agitation → delirium)
• Hyperthermia
• Autonomic instability (tachycardia, hypertension, diaphoresis)
• Hyperreflexia and clonus (especially lower limbs)
• Muscle rigidity
• Deaths have been reported

4. CNS Excitation

• Agitation, tremor, hallucinations
• This is the SNRI and serotonergic component, distinct from the opioid component

5. Other Complications

• Hypoglycaemia — tramadol is associated with higher rates of hypoglycaemia than codeine, especially within the first 30 days of use (mechanism unclear)
• Rhabdomyolysis, compartment syndrome, myoglobinuric renal failure (especially post-seizure)
• Acute lung injury (non-cardiogenic pulmonary oedema) — uncommon; presents with tachypnoea, hypoxia, bilateral infiltrates
• Dependence and withdrawal — reported with chronic use; tramadol should be tapered before discontinuation

High-Risk Drug Interactions

Special Populations

• Paediatric patients: Tramadol is contraindicated in children <12 years and for post-tonsillectomy/adenoidectomy pain in patients <18 years (same FDA black box warning as codeine). Contraindicated in breastfeeding mothers due to risk of infant death.
• CYP2D6 ultrarapid metabolisers: Produce excessive M1 → greater opioid toxicity
• Epilepsy: Tramadol is relatively contraindicated
• Renal/hepatic impairment: Impaired clearance of tramadol and M1

Diagnosis

• Diagnosis is primarily clinical
• Standard urine opioid immunoassays typically do NOT detect tramadol (these screens detect morphine-class opioids; tramadol requires specific GC/MS or HPLC confirmation)
• Check: blood glucose, renal function, CK (if seizures occurred), ECG, paracetamol level (if co-ingestion suspected)
• Consider serotonin syndrome criteria (Hunter or Sternbach)

Management

Immediate Priorities

1. Airway, Breathing, Circulation — respiratory depression is the primary cause of death
2. Oxygen and bag-valve-mask ventilation as needed
3. Endotracheal intubation if respiratory depression is unresponsive to naloxone or if acute lung injury is suspected

Decontamination

• Activated charcoal (1 g/kg PO) — may be given within 1–2 hours of ingestion in a cooperative patient with intact airway reflexes; with caution given CNS depression risk

Naloxone

• Partially reverses tramadol's opioid effects (respiratory depression, sedation)
• Does NOT prevent or treat seizures
• May precipitate/worsen seizures — use cautiously, titriting to respiratory effect rather than full reversal
• Dosing (Tintinalli's, Table 186-3):

• Duration of naloxone (20–90 min) is often shorter than tramadol/M1 half-life → naloxone infusion may be required

Seizures

• Benzodiazepines (e.g. diazepam, lorazepam) are first-line
• Tramadol seizures are usually single and self-limiting — routine prophylactic anticonvulsants are not necessary
• Avoid physostigmine; naloxone does not help

Serotonin Syndrome

• Discontinue tramadol and all serotonergic drugs
• Benzodiazepines for agitation and muscle rigidity
• Active cooling for hyperthermia
• Cyproheptadine (serotonin antagonist) as adjunct
• Severe cases: consider chlorpromazine or methysergide; intubation, paralysis, and ICU care if temperature >41°C or haemodynamic instability

Disposition

• All significant tramadol overdoses warrant monitoring for a minimum of 6–8 hours (longer for extended-release formulations)
• Admit for seizures, respiratory compromise, persistent altered consciousness, or serotonin syndrome features

Summary: What Makes Tramadol Poisoning Unique

Vacutainers — Complete Guide

Tube Colours, Additives & Uses

Which Tube Must Be Kept Moving (Gently Inverted)?

The tube that must be kept moving most critically is the EDTA tube (Lavender/Purple)

• EDTA binds calcium and prevents clotting, but only if thoroughly mixed with blood
• If not mixed immediately, micro-clots form → falsely low platelet count, falsely elevated WBC, and invalid CBC results
• Must be inverted 8 times gently (not shaken — shaking causes haemolysis)

Required inversions for each tube type (Tietz, Table 4-2):

"It is critical that complete mixing of any additive with the blood collected be accomplished as quickly as possible. Completing a blood collection within 2 minutes of starting, and getting the tubes mixed correctly as soon as possible, helps to prevent clotting in anticoagulated tubes." — Tietz Textbook of Laboratory Medicine, 7th Edition

Order of Draw (When Multiple Tubes Are Collected)

General rule: No additive → mild anticoagulant → strong anticoagulant

Serum vs Plasma — Practical Points

Vacutainer Tubes — Quick Reference

Which Tube Must Be Kept Moving?

Why?

• Falsely low platelet count
• Invalid CBC/FBC results

Required inversions (gentle, not shaking):

Order of Draw

Plain Red Tube (No Additive — Glass)

• No additive to mix in → no reason to invert
• The clot forms naturally within 30–60 minutes
• Gentle inversion won't prevent or accelerate clotting in any meaningful way

Red/Gold SST Tube (Serum Separator Tube — with Clot Activator + Gel)

• If you don't invert → incomplete clotting → fibrin strands remain → interfere with gel separation → invalid results
• If you over-invert or shake → haemolysis → falsely elevated potassium, LDH, AST

Key Practical Points

Bottom Line

• Plain red glass tube: inverting it won't damage the sample, but it serves no purpose
• SST (gold or red-black): must be inverted exactly 5 times — not more, not less
• Vigorous shaking of any tube is the real danger — it causes haemolysis regardless of tube type