Skip to main content

HYPERTHERMIA SYNDROMES- 4: DRUG INDUCED HYPERTHERMIA

"The fact that patient gets well, does not prove that diagnosis was correct"
                                                                 - Samuel J. Meltzer

SEROTONIN SYNDROME (SS):
SS is characterized by hyperthermia, altered mentation, mydriasis, increased muscle tone, hyperreflexia, clonus, diarrhea and autonomic instability, developing 6-12 hours after exposure to serotonin agonist agents.

There is prominent diaphoresis and sialorrhea.

Clonus is the most specific sign of SS.

Drugs associated with SS are:
  • Selective serotonin reuptake inhibitors (SSRI)- fluoxetine, sertraline, citalopram, escitalopram,
  • Serotonin norepinephrine reuptake inhibitors (SNRI)- venlafaxine, duloxetine, 
  •  TCA- clomiperamine, imipramine, trazodone,
  • MAO inhibitors- selegiline, procarbazine, linezolid, furazolidone,
  • Opiates- meperidine, tramadol, fentanyl, dextromethorphan, pentazocine, dextropropxyphene,
  •  Antiemetics- ondansetron, granisetron, metocloperamide,
  •  Antihistamines- chlorpheniramine,
  •  Antimigraine drugs- triptans,
  • Supplemental /Herbal dietary products- St. John’s wort, tryptophan, 5 hydroxytryptophan, ginseng,
  • Stimulants- amphetamine, 3,4-methylenedioxymetamphetamine (ecstasy),
  • Psychedelics- lysergic acid diethylamide (LSD).

Of these fentanyl, tramadol, linezolid, ondansetron, granisetron, metocloperamide and chlorpheniramine are commonly used drugs in ICU.

PATHOPHYSIOLOGY: Excessive stimulation of postsynaptic 5HT1A and 5HT2A receptors by serotonergic agents has been implicated in SS.

SS is classically associated with simultaneous administration of two serotonergic agents, but can occur with single serotonergic agent or with dose escalation.

True incidence of SS is not known probably because of underdiagnosis, but has been reported in around 14% cases of SSRI overdose.

DIAGNOSIS: Diagnosis is established using Hunter Serotonin toxicity criteria.  Presence of any of the following, with history of exposure to serotonergic drug, establishes diagnosis of SS:

1.      Spontaneous clonus; or
2. Inducible clonus or ocular clonus and agitation or diaphoresis; or
3. Inducible clonus or ocular clonus and increased muscle tone and temperature more than 38˚C; or
4.     Tremors and hyperreflexia.

Symptoms usually evolve over 6-12 hours of exposure to serotonergic drugs and resolve within 24 hours of discontinuation of offending agent.

But fluoxetine and other long acting drugs may produce prolong course.

TREATMENT:
Discontinuation of all serotonergic medication is the mainstay of therapy.

External cooling should be established as early as possible.

ABC (Airway, breathing and circulation) should be assessed and managed accordingly, including endotracheal intubation if needed. Intravascular volume should be optimized to ensure organ perfusion and prevent complications of rhabdomyolysis.

Benzodiazepines may reduce agitation and hypertonicity. Intubated patients should be optimally sedated with midazolam.

Definitive therapy involves serotonin antagonist, cyproheptadine (antihistamine with 5HT1A, 5HT2A receptor antagonist activity). It is administered as 12 mg stat dose, followed by 2 mg every 2 hourly until symptoms resolve, then 8 mg every 6 hourly.

Cyproheptadine may cause sedation, which helps in reducing agitation. It may also precipitate hypotension, which may respond to fluid boluses.

Chlorpromazine, antipsychotic with 5HT2A receptor antagonist activity, may be used as alternative to cyproheptadine. It is given as 50-100 mg intramuscular injection, and repeated every 6 hourly if needed.

Propranolol should not be used, to control adrenergic symptoms and hypertension, as it also has 5HT1A receptor antagonist activity, and can precipitate hypotension. Other long acting beta blocker should also be avoided. Short acting agents like esmolol may be used to control blood pressure.

In case of exposure to MAO inhibitors and hypotension, dopamine should be avoided, because of the risk of exaggerated hemodynamic response. Noradrenaline or phenylephrine may be used.

NMS and SS must not be confused with other, as definitive treatment is entirely different. Bromocriptine (dopamine agonist) administered for mistaken diagnosis of NMS, may worsen SS. Similarly chlorpromazine (dopamine antagonist) given for erroneous diagnosis of SS, may worsen NMS.

Neuroleptic malignant syndrome
Serotonin syndrome
Onset
Variable, 1-3 days
Variable, < 12 hours
Overlapping
Features
Diaphoresis
Pallor
Diaphoresis
Variable, stupor, coma, alert
Variable, agitation, coma
'Lead-pipe' rigidity in all muscle groups
Increased tone,
especially in lower extremities
Distinct Features
Hyporeflexia
Hyperreflexia
Clonus  
Normal pupils
Dilated pupils
Normal or decreased bowel sound
Hyperactive bowel sounds

                

Comments

Post a Comment

Popular posts from this blog

FROM BICARBONATE TO STRONG ION DIFFERENCE- INTRIGUING STORY OF BLOOD ACID-BASE ANALYSIS   “Life is struggle, not against sin, not against money power…. but against Hydrogen ion.” - H.L. Mencken, 1919   Since the understanding of similarity between fermentation of wine and respiration of animals, evolution of human physiology and measurement of carbon dioxide is coupled with studies of acids and bases. Alkalinity of blood was demonstrated by color indicators as early as eighteenth century by French chemist Hilaire Marin Rouelle, and one century later, its relation with gastric acid secretion was recognized by Henry Bence Jones. In 1831, William B. O’Shaughnessy, an Irish physician working in India, demonstrated that Cholera reduced the free alkali of blood. But the discovery of relationship between blood alkalinity and carbon dioxide was contained within the mystery of diabetic coma.   1.     Story of Carbon Dioxide and Alkalinity of blood   In Nineteen...
Post a Comment
Read more

Vocal Cord Dysfunction (VCD ) or PARADOXICAL VOCAL CORD MOVEMENT (PVCM)

▪Inappropriate adduction of true vocal cords, mostly during inspiration. This results in dyspnoea and strider during inspiration. Rarely it may happen during expiration also. ▪15 Y F presenting with acute respiratory distress for 48 hours. For the past 2 years she was on inhaled bronchodialtors and steroids with short cources of oral/IV steroids for bronchial asthma. There was history of 4 hospital admissions and several emergency visits for symptoms attributed to asthma. Examination revealed apprehensive, tachycardic, tachpnoic girl with accessory muscle use and widespread rhonchi bilaterally, SPO2 93% on room air. Other systemic examination were normal. She was started on inhalation therapy but her conditioned worsened. Oxygen saturation felled to 78% ON 10 L face mask,  ABG revealed pH 7.53, PaO2 58, PaCO2 28. She was intubated emergency and shifted TO ICU. She was treated as life threatening attack of bronchial asthma. She improved dramatically and successfully e...
Post a Comment
Read more

REVERSE TRIGGERING: A newly classified though common form of double triggering

Reverse triggering is a recently defined type of double triggering where a controlled mechanical breath, stimulates receptors in the lung, eliciting inspiratory effort. Seen in patients who are deeply sedated with high mechanical ventilation rates. Reverse triggering could be explained by respiratory entrainment, a form of patient ventilator interaction, where diaphragmatic muscle contraction is triggered by ventilator insufflations, leading to breath initiation. Consequences of reverse triggering are large. Continuously induced muscle contraction of diaphragm cause cytokine release and muscle fibre damage. Additionally it increases inspiratory muscle load and oxygen consumption and may lead to cardiovascular instability. Reverse triggering also makes measurement of plateu pressure misleading as well as may generate high platue pressure and ventilator induced lung injury. Management is not entirely clear. Increasing sedation does not help. Increasing inspiratory time will cause the...
Post a Comment
Read more