Serotonin Syndrome (Clinical)

Overview

Definition^[4]

Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome is a potentially life-threatening condition caused by large increases in serotonergic activity Serotonergic Activity Serotonin Syndrome due to exposure to serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS agonists. Defining symptoms include altered mental status Altered Mental Status Sepsis in Children, autonomic instability Autonomic instability Rabies Virus, and neuromuscular abnormalities (tremors, myoclonus Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome. Neurological Examination).

Epidemiology^[4,6]

• Exact incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is unknown due to:
  • Lack of confirmatory testing
  • Wide spectrum of severity
• Cases appear to be increasing:
  • Increased awareness of disease by providers
  • Increased use of serotonergic medication

Etiology^[6]

Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome occurs secondary to use of therapeutic medication, drug interactions, or overdose.

• Psychiatric drugs:
  • Selective serotonin reuptake inhibitors Selective Serotonin Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SSRIs SSRIs Serotonin Reuptake Inhibitors and Similar Antidepressants): most common cause
  • Serotonin-norepinephrine reuptake inhibitors Serotonin-Norepinephrine Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants)
  • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS modulators (e.g., trazodone Trazodone A serotonin uptake inhibitor that is used as an antidepressant agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. Serotonin Reuptake Inhibitors and Similar Antidepressants)
  • Monoamine oxidase Oxidase Neisseria inhibitors (e.g., tranylcypromine Tranylcypromine A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. Monoamine Oxidase Inhibitors, phenelzine Phenelzine One of the monoamine oxidase inhibitors used to treat depression; phobic disorders; and panic. Monoamine Oxidase Inhibitors, isocarboxazid Isocarboxazid An mao inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. Monoamine Oxidase Inhibitors, selegiline Selegiline A selective, irreversible inhibitor of type B monoamine oxidase that is used for the treatment of newly diagnosed patients with parkinson disease, and for the treatment of depressive disorders. Monoamine Oxidase Inhibitors)
  • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants ( TCAs TCAs Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants)
  • Buspirone
• Nonpsychiatric drugs:
  • Tramadol Tramadol A narcotic analgesic proposed for severe pain. It may be habituating. Opioid Analgesics
  • Dextromethorphan
  • Metoclopramide Metoclopramide A dopamine d2 antagonist that is used as an antiemetic. Antiemetics 
  • Linezolid Linezolid An oxazolidinone and acetamide derived anti-bacterial agent and protein synthesis inhibitor that is used in the treatment of gram-positive bacterial infections of the skin and respiratory tract. Oxazolidinones
• Illicit drugs Illicit Drugs Drugs that are manufactured, obtained, or sold illegally. They include prescription drugs obtained or sold without prescription and non-prescription drugs. Illicit drugs are widely distributed, tend to be grossly impure and may cause unexpected toxicity. Delirium:
  • MDMA MDMA An n-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as mdma or ecstasy. Stimulants (3,4-Methyl​enedioxy​ methamphetamine Methamphetamine A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Stimulants, ecstasy Ecstasy An n-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as mdma or ecstasy. Stimulants, or molly)  
  • LSD (lysergic acid diethylamide)
  • Amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants
  • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
• Supplements/herbal medication:
  • St. John’s wort
  • Tryptophan

Pathophysiology

Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome occurs from any combination of drugs that have the net effect of increasing serotonergic neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission.^[5,6,10]

• Stimulation of postsynaptic 5-HT1A and 5-HT2A receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
• Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS ( 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS) receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors normally found in the CNS regulate:
  • Attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment
  • Behavior
  • Thermoregulation Thermoregulation Body temperature can be divided into external temperature, which involves the skin, and core temperature, which involves the CNS and viscera. While external temperature can be variable, the core temperature is maintained within a narrow range of 36.5-37.5ºC (97.7-99.5ºF). Body Temperature Regulation
• Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS ( 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS) receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors found in the peripheral nervous system Peripheral nervous system The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. Nervous System: Anatomy, Structure, and Classification (PNS) regulate:
  • GI motility GI Motility The primary functions of the GI tract are digestion and absorption, which require coordinated contractions of the smooth muscles present in the GI tract. Peristaltic waves, segmentation contractions, and the migrating motor complex are all important contraction patterns that help to mix contents, get them in contact with the intestinal walls, and propel material down the tract at appropriate times and in appropriate amounts. Gastrointestinal Motility
  • Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Uterine contraction
  • Bronchoconstriction

Clinical Presentation

Neuromuscular hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder^[1,4,5]

• Hyperreflexia
• Myoclonus Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome. Neurological Examination
• Mental status changes
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma
• Tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies

Autonomic dysregulation Autonomic Dysregulation Neuroleptic Malignant Syndrome^[1,4,5]

• Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, arrhythmias
• Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
• Unstable blood pressures (usually elevated)
• Diaphoresis
• Hyperthermia
• Mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma
• Dry mucous membranes
• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions flushing
• Shivering Shivering Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. Body Temperature Regulation

Gastrointestinal stimulation^[4,5]

• Increased bowel sounds
• Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea

Symptom severity^[5,7]

Assessing the severity of the patient’s presentation will help guide management.

Mnemonic

MADAM’S TIPS:

• Mental status change
• Agitation
• Diarrhea
• Ataxia
• Myoclonus
• Shivering
• Tachycardia
• Increased reflexes
• Pyrexia
• Sweating

Diagnosis

Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome is clinically diagnosed (serum serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS levels have no correlation Correlation Determination of whether or not two variables are correlated. This means to study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable. Causality, Validity, and Reliability to symptoms or toxicity Toxicity Dosage Calculation).^[4] Multiple diagnostic criteria have been developed, with the Hunter Serotonin Toxicity Criteria Hunter Serotonin Toxicity Criteria Serotonin Syndrome being the most accurate.

Hunter Serotonin Toxicity Criteria Hunter Serotonin Toxicity Criteria Serotonin Syndrome^[2]

Patient must have taken a serotonergic drug and be positive for 1 of the following criteria:

• Spontaneous clonus Clonus Ehrlichiosis and Anaplasmosis
• Inducible clonus Clonus Ehrlichiosis and Anaplasmosis + agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus or diaphoresis
• Ocular clonus Clonus Ehrlichiosis and Anaplasmosis + agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus or diaphoresis
• Tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies + hyperreflexia
• Hypertonia Hypertonia Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. Neurological Examination + hyperthermia (> 38°C (> 100.4°F)) + ocular/inducible clonus Clonus Ehrlichiosis and Anaplasmosis

Management

Management may vary depending on local practice guidelines. The following information is based on North American and UK literature.

Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome often resolves within 24 hours of discontinuing the serotonergic agent and initiating care.

Treatment setting

• Mild cases generally resolve within 24–72 hours with conservative therapy and removal of the causative agent.^[4]
• Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship do not require hospitalization Hospitalization The confinement of a patient in a hospital. Delirium.
• Mild cases should be observed for ≥ 6 hours before discharge.^[5]
• Admission is recommended for moderate to severe cases with:^[4,5]
  • Hypertonicity Hypertonicity Volume Depletion and Dehydration
  • Hyperthermia 
  • Autonomic instability Autonomic instability Rabies Virus 
  • Progressive cognitive changes
  • Complications

Supportive care

• Discontinuation of all serotonergic agents^[5]
• Control fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever:
  • Cooling blankets
  • Ice packs
  • Note: Antipyretics are generally not useful. 
• Oxygen
• IV fluid hydration
• Continuous cardiac monitoring^[5]
• Avoid physical restraints, when possible^[7]
• Severe cases may potentially require any of the following (particularly if temperature is > 41℃):^[4,5,11]
  • Intubation Intubation Peritonsillar Abscess
  • Sedation
  • Nondepolarizing neuromuscular blocking agents

Medical management

• Benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines may be given for the management of:^[4,5]
  • Agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Mild hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children 
  • Tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies
• Antidote Antidote An antidote is a substance that counteracts poisoning or toxicity. Substances that can cause poisoning include heavy metals (from occupation, treatments, or diet), alcohols, environmental toxins, and medications. Antidotes of Common Poisonings therapy: cyproheptadine Cyproheptadine A serotonin antagonist and a histamine h1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. Serotonin Syndrome (5-HT2 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonist):^[4,9]
  • Given if benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines do not improve signs and symptoms, usually in moderate or severe cases
  • Initial dose: 12 mg, followed by additional 2 mg every 2 hours if symptoms continue
  • Once the person is stabilized, consider a maintenance dose Maintenance Dose Dosage Calculation of 8 mg every 6 hours. 
  • Note: Cyproheptadine Cyproheptadine A serotonin antagonist and a histamine h1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. Serotonin Syndrome does not shorten serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome’s course.^[5]
• Severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension and tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children can be managed with:^[1,5]
  • Esmolol Esmolol Antiadrenergic Drugs
  • Nitroprusside Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitrates

Potential complications^[8]

• Rhabdomyolysis Rhabdomyolysis Rhabdomyolysis is characterized by muscle necrosis and the release of toxic intracellular contents, especially myoglobin, into the circulation. Rhabdomyolysis and myoglobinuria Myoglobinuria The presence of myoglobin in urine usually as a result of rhabdomyolysis. Rhabdomyolysis
• Disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation ( DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation)
• Metabolic acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
• Acute renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
• ARDS

Differential Diagnosis

It is important to distinguish between serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome, malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia, and neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome.

• Neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome ( NMS NMS Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome): rare, idiosyncratic, and potentially life-threatening reaction to neuroleptic (e.g., antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics) drugs. Very similar to serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome, but without the GI symptoms and more muscle rigidity Muscle rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Motor Neuron Lesions. Treated similarly to serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS syndrome, by discontinuing causative drugs and offering supportive care. 
• Malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia: rare complication triggered by certain inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts or paralytics. Suspect in operating room or anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts procedure. Treatment is nearly the same as NMS NMS Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome and clinically indistinguishable except for drugs triggering the syndrome.