Febrile Seizures

febrile seizures

A 20 Month-Old Male

It is a busy Wednesday afternoon in your pediatric emergency department. You work at a tertiary center, so you are used to receiving transfers from other hospitals for further evaluation and management. You see a new patient on the board. It is a 20 month-old male who came in as a hospital transfer for evaluation of first-time seizure. You go to bedside to start your evaluation. Parents tell you that he had three episodes of seizures in the past 6 hours. All of them lasted for less than 15 minutes, did not require medication for cessation, one of them was described as partial-focal and two were described as generalized tonic-clonic seizures, and the patient had complete return to baseline behavior a few minutes after each episode. Mom says that the patient had his axillary temperature taken by her at home and by the staff at the outside hospital and he had no fever on these measurements. However, she did notice some runny nose in the past 24 hours. As soon as the mom tells you that information, the nurse looks at you and says that the patient’s rectal temperature is 40.1 C.

Febrile Seizures

The first-step in the management of febrile seizures is to understand its definitions. Following that, we need to appropriately classify the patient’s presentation within one of the two types of febrile seizure.

Definition

  • Age greater than six-months-old and lower than five-years-old
  • Seizure in a patient with a temperature higher than 38 C
  • No inflammation or infection of the central nervous system
  • No metabolic abnormality that may cause seizures
  • No history of afebrile seizures

Two Types of Febrile Seizures

Class Age Number of seizures in 24h Duration Type of seizure Resolution Return to baseline
Simple
6 mo to 5 yo
1
< 15 min
No focal features
No meds required
Yes
Complex
6 mo to 5 yo
> 1
> 15 min
Focal features
Med required
No return to baseline in a reasonable time

You must note that you will be able to easily identify those patients who fit the criteria for simple febrile seizures and those who fit the criteria for complex febrile seizures. However, there will be a group of patients that fill one or two criteria for complex febrile seizure, but are extremely well-appearing. We will talk more about that later on during the discussion.

Workup

Simple Febrile Seizures

The evaluation of a child with a simple febrile seizure should focus on the underlying febrile illness. In the vast majority of the cases the cause for the fever will be a viral infection that does not require further evaluation and treatment other than some acetaminophen (paracetamol), ibuprofen, and oral hydration.

However, as part of your job, you need to think outside of the box and have a broad differential diagnosis for your patient’s presentation. Make sure to rule out signs of CNS infection (altered mental status, nuchal rigidity, petechial rashes, and prolonged, focal or multiple seizures); risk factors, symptoms, and signs of systemic conditions that could be causing a seizure; and, history of afebrile seizures. Special factors that increase the risk for CNS infections and that you should consider in your evaluation are age 6 -12 months with incomplete immunization status (Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae) and pre-treatment with antibiotics for another disorder (which could mask meningitis).

Complex Febrile Seizure in Ill-Appearing Child

The workup in this situation is simple. The patient has meningitis until proven otherwise. You should consider starting antibiotics immediately and obtaining a full sepsis workup including complete blood cell count, urinalysis, urine culture, blood cultures, chest x-ray, and lumbar puncture for cerebrospinal fluid analysis. In addition to the infectious work-up, the differential also includes epileptic seizures, toxic ingestion, metabolic disorders, head trauma, and intracranial hypertension.

Complex Febrile Seizure in Well-Appearing Child

Now we reached the tricky part of the discussion. There are no consensus guidelines for the workup of patients with complex febrile seizures in the well-appearing child. As stated in the simple febrile seizure section, you should consider further workup if any concerns for CNS infection, systemic conditions causing seizures, or history of afebrile seizures. You should decide which workup to perform on a case by case basis. In a perfect scenario, these cases should be evaluated in conjunction with specialist consultation (e.g. with pediatric neurology) for guidance with work-up and treatment.

Case Resolution

After you finish your assessment, you make the diagnosis of complex febrile seizure because the patient had multiple seizures in less than 24 hours and had one episode with focal features. The patient is well-appearing, is fully vaccinated, has not used antibiotics recently, returns to baseline completely soon after an episode, and has no findings concerning for CNS infection on his exam. Therefore, you think that a CNS infection is less likely. Since you are facing a case of complex febrile seizure in a well-appearing child, you consult pediatric neurology for guidance with the workup and treatment. They agree with the low likelihood of CNS infection and recommend symptomatic treatment for the patient’s likely upper respiratory infection with observation during six hours in the ED. The patient has no problems during the period of observation. You re-discuss the case with pediatric neurology and they recommend discharge home with close follow-up on their clinic for further workup of other causes of seizure. A couple days later, you check the patient’s records and find that he had a spot EEG done, which was negative for epileptiform waves, and a brain MRI performed, which was unremarkable. Patient was diagnosed with complex febrile seizure and recommended to keep follow-up with his primary care physician with no need for further follow-up with pediatric neurology.

Take-Home Points

  • Always obtain a temperature from a core source, in the ED the most feasible source is a rectal temperature
  • The differential diagnosis for febrile seizures includes CNS infections, epileptic seizures, toxic ingestion, metabolic disorders, head trauma, and intracranial hypertension
  • There is no consensus about the workup and treatment of the well-appearing patient with a complex febrile seizure

References and Further Reading

  1. Festekjian A. Seizures and Status Epilepticus in Children. In: Cydulka RK, Fitch MT, Joing SA, Wang VJ, Cline DM, Ma O. eds. Tintinalli’s Emergency Medicine Manual, 8e New York, NY: McGraw-Hill; . http://accessemergencymedicine.mhmedical.com/content.aspx?bookid=2158§ionid=162271372. Accessed May 12, 2019.

  2. https://www.emrap.org/episode/kiddos/febrileseizures

  3. https://www.emrap.org/episode/c3seizuresin/seizuresin 

  4. John J Millichap. Clinical features and evaluation of febrile seizures. Mar 25, 2019. https://www.uptodate.com/contents/clinical-features-and-evaluation-of-febrile-seizures?source=history_widget

Cite this article as: Henrique Puls, Brasil, "Febrile Seizures," in International Emergency Medicine Education Project, September 9, 2019, https://iem-student.org/2019/09/09/febrile-seizures/, date accessed: July 6, 2022

A 32-year-old male with anxiety and tremor

You are working an evening shift during your first year as an Emergency Medicine resident. A new patient shows up on the board. You briefly check his information, and you learn that he is a 32-year-old male with history of alcohol abuse coming into the Emergency Department for anxiety and tremors.

Triage note says in bold: “last drink 50 hours ago.” The patient is tachycardic, hypertensive, and mildly tachypneic. 

You go to see the patient and based on the information you got, you diagnose him with alcohol withdrawal syndrome complicated by withdrawal delirium (delirium tremens). Good! You have a clinical diagnosis, but what does this patient need for workup and management?

Figure 1. DSM-5 Criteria for Alcohol Withdrawal and Delirium. If the patient fulfills the criteria for both the diagnosis of alcohol withdrawal complicated by withdrawal delirium is made.

Pathophysiology

There are two different ethanol action in the central nervous system (CNS) that lead to symptoms of alcohol withdrawal. Overall, alcohol is a central nervous system depressant. It simultaneously increases inhibitory tone via modulation of GABA activity and decreases excitatory tone via modulation of excitatory amino acid activity. In a patient with alcohol abuse disorder, only a constant presence of alcohol keeps the necessary homeostasis. Sudden cessation unmasks the adaptive responses to chronic ethanol use, resulting in overactivity of the central nervous system.

Gamma-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. Highly specific binding sites for ethanol are found on the GABA receptor complex. Chronic ethanol use induces GABA receptor insensitivity to GABA resulting in a need for a stronger inhibitory stimulus to maintain a constant inhibitory tone. As alcohol tolerance develops, the individual retains arousal at alcohol concentrations that would normally produce lethargy or even coma in people who do not have alcohol use disorder. Sudden cessation of alcohol intake or a reduction from chronically elevated concentrations results in decreased inhibitory tone due to the lack of inhibitory effects of ethanol.

Glutamate is one of the major excitatory amino acids. When glutamate binds to the N-methyl-D-aspartate (NMDA) receptor, calcium influx leads to neuronal excitation by binding to the glycine receptor on the NMDA complex. Ethanol inhibits glutamate-induced excitation. Adaption occurs by increasing the number of glutamate receptors in an attempt to maintain a normal state of arousal.

Figure 2. Inhibitory and excitatory balance in a healthy individual.
Inhibitory and excitatory balance in an individual with chronic alcohol abuse.
Figure 3. Inhibitory and excitatory balance in an individual with chronic alcohol abuse. The constant presence of alcohol is needed to maintain inhibitory tone on insensitive GABA receptors and to inhibit excitatory tone on upregulated NMDA receptors.
Loss of the inhibitory and excitatory balance after alcohol cessation.
Figure 4. Loss of the inhibitory and excitatory balance after alcohol cessation. Upregulated NMDA receptors lead overexcitation, and insensitive GABA receptors are not enough to counteract that. Alcohol withdrawal symptoms ensue.

Differential Diagnosis

Alcohol withdrawal remains a clinical diagnosis. The severity of presentation can be assessed using a clinical assessment scale called Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) that can be found on MD Calc.

In some cases, several additional tests might be needed to rule out other conditions that mimic or coexist with alcohol withdrawal syndrome. This is especially true when the patient has altered mental status and fever. Conditions such as infection (e.g., meningitis), trauma (e.g., intracranial hemorrhage), metabolic abnormalities, drug overdose, hepatic failure, and gastrointestinal bleeding can mimic or coexist with alcohol withdrawal. Also, it is of marked importance to try to understand why the patient stopped consuming alcohol. If you establish that he wanted to get sober, that is great, you or the admitting team can help setting up rehab for him after the acute problems are controlled. However, you should get suspicious if there is not a clear cause for the abrupt cessation of alcohol intake since it could be an acute condition being masked by the withdrawal syndrome.

Initial workup might include:

  • Point of care glucose

  • CBC and platelets

  • Sodium, potassium, chloride, bicarbonate, BUN, creatinine

  • Calcium, magnesium, and phosphorus

  • Total protein, albumin, total bilirubin, AST, ALT, and alkaline phosphatase, and lipase

  • Creatine kinase

  • Chest x-ray to rule out simultaneous pneumonia

  • Consider head CT and lumbar puncture, if there are any findings concerning for trauma, intracranial hemorrhage, or CNS infections

  • Consider drug screen if concern for co-ingestion

Figure 5. The differential diagnosis for alcohol withdrawal. It is important to not anchor on this diagnosis and to look for mimics and conditions that might coexist with it.

Supportive Care

As important as proving control of the patient’s withdrawal symptoms is to provide high-quality supportive care, which includes:

  • Placement in a quiet and protective environment

  • Preference for chemical sedation over physical restraints, which should be removed as soon as adequate chemical sedation is achieved because resistance against restraints can increase temperature, produce rhabdomyolysis, and cause physical injury

  • IV fluids

  • Thiamine and glucose should be administered in order to prevent or treat Wernicke encephalopathy

  • Multivitamins containing or supplemented with folate should be given routinely

  • Deficiencies of glucose, potassium, magnesium, and phosphate should be corrected as needed

  • Nothing by mouth in the early stages of treatment to prevent aspiration

  • Patients considered at high risk for complications should be monitored in an intensive care unit

  • Consider ICU admission and EtCO2 monitoring in those patients with severe alcohol withdrawal per CIWA-Ar

Symptomatic Treatment

The basis for the treatment of alcohol withdrawal is CNS depressants, such as benzodiazepines, with a treatment goal of Richmond Agitation and Sedation Scale (RASS) -1 and HR < 110. No single drug benzodiazepine is superior to another. A common treatment strategy is to use a benzodiazepine of choice and give escalating doses until symptomatic control or until you reach criteria for refractory alcohol withdrawal.

Figure 6. Two common initial treatment strategies for alcohol withdrawal.

Refractory Withdrawal Delirium

Some patients have refractory delirium tremens (DT) despite treatment with high-dose benzodiazepines. Refractory DT is not clearly defined. It may be present if symptoms of severe withdrawal are not controlled adequately after the IV administration of more than 50 mg of diazepam or 10 mg of lorazepam during the first hour of treatment, or 200 mg of diazepam or 40 mg of lorazepam during the initial three to four hours of treatment. In such cases, as with any dangerous toxicologic disorder, you should obtain assistance from a medical toxicologist or poison control center. In case you diagnose your patient with alcohol withdrawal refractory to benzodiazepine treatment, you should have a few other options in your treatment arsenal.

Summary of sedation strategy.
Figure 7. Summary of sedation strategy. Initial treatment with benzodiazepines in escalating doses. If good response, keep regimen titrated to treatment goals. If no response, consider refractory withdrawal delirium and other pharmacologic options. If no response after secondary treatment, consider intubation with propofol.

Phenobarbital

There are case reports of up to 2000 mg of Phenobarbital administered orally or intravenously on the first day in patients with alcohol withdrawal delirium. Consider giving phenobarbital 130 to 260 mg IV, repeated every 15 to 20 minutes, until symptoms are controlled. Also, you can consider administering Phenobarbital earlier in the disease course. A randomized trial of 102 patients presenting to the emergency department with acute alcohol withdrawal, those treated with lorazepam and a single dose of Phenobarbital had substantially lower ICU admission rates compared with those treated with lorazepam alone (8 versus 25 percent).

Dexmetomedine

Another adjunctive medication for alcohol withdrawal is dexmedetomidine, an α2-adrenergic agonist that is used to provoke a state in which the patient is sedated but arousable, with a decreased sympathetic tone. Doses up to 0.7 μg per kilogram per hour have been administered in patients who do not have a good response to benzodiazepines. Heart block is a contraindication to this drug since it can cause bradycardia. In case it is given, blood pressure and heart rate must be closely monitored.

Propofol and Intubation

In patients who do not have a response to high doses of benzodiazepines (especially patients who are intubated), propofol may be administered to reach symptomatic control.

Take home points.
Figure 8. Take home points.

Further Reading

References

  • Isbell H, Fraser HF, Wilker A, et al. An experimental study of the etiology of rum fits and delirium tremens. Q J Stud Alcohol 1955; 16:1.
  • Mihic SJ, Ye Q, Wick MJ, et al. Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 1997; 389:385.
  • Morrow AL, Suzdak PD, Karanian JW, Paul SM. Chronic ethanol administration alters gamma-aminobutyric acid, pentobarbital and ethanol-mediated 36Cl- uptake in cerebral cortical synaptoneurosomes. J Pharmacol Exp Ther 1988; 246:158.
  • Hoffman PL, Grant KA, Snell LD, et al. NMDA receptors: role in ethanol withdrawal seizures. Ann N Y Acad Sci 1992; 654:52.
  • Hecksel KA, Bostwick JM, Jaeger TM, Cha SS. Inappropriate use of symptom-triggered therapy for alcohol withdrawal in the general hospital. Mayo Clin Proc 2008; 83:274.
  • Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA 1998; 279:583.
  • Hoffman RS, Goldfrank LR. The poisoned patient with altered consciousness. Controversies in the use of a ‘coma cocktail’. JAMA 1995; 274:562.
  • Hoffman RS, Goldfrank LR. Ethanol-associated metabolic disorders. Emerg Med Clin North Am 1989; 7:943.
  • Mainerova B, Prasko J, Latalova K, et al. Alcohol withdrawal delirium — diagnosis, course and treatment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013;157:1-9
  • Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium: an evidence-based practice guideline. Arch Intern Med 2004;164:1405-1412
  • Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev2010;3:CD005063-CD005063
  • Hjermø I, Anderson JE, Fink-Jensen A, Allerup P, Ulrichsen J. Phenobarbital versus diazepam for delirium tremens — a retrospective study. Dan Med Bull 2010;57:A4169-A4169
  • DeCarolis DD, Rice KL, Ho L, Willenbring ML, Cassaro S. Symptom-driven lorazepam protocol for treatment of severe alcohol withdrawal delirium in the intensive care unit. Pharmacotherapy 2007;27:510-518
  • DeBellis R, Smith BS, Choi S, Malloy M. Management of delirium tremens. J Intensive Care Med 2005;20:164-173
  • Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 2003; 63:53.
  • Nolop KB, Natow A. Unprecedented sedative requirements during delirium tremens. Crit Care Med 1985; 13:246.
  • Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: does an unexpectedly large sedative requirement identify these patients early? J Med Toxicol 2006; 2:55.
  • Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med 2013; 44:592.
  • Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care 2012;2:12-12
  • Muzyk AJ, Fowler JA, Norwood DK, Chilipko A. Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother 2011;45:649-657
  • Thomson AD, Cook CCH, Touquet R, Henry JA. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department. Alcohol Alcohol 2002;37:513-521
  • Koethe D, Juelicher A, Nolden BM, et al. Oxcarbazepine — efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. Alcohol Clin Exp Res 2007;31:1188-1194
Cite this article as: Henrique Puls, Brasil, "A 32-year-old male with anxiety and tremor," in International Emergency Medicine Education Project, June 3, 2019, https://iem-student.org/2019/06/03/a-32-year-old-male-with-anxiety-and-tremor/, date accessed: July 6, 2022