Majaczenie jako powikłanie nikotynowego zespołu abstynencyjnego: opis przypadku

■ Introduction

There are 1.1 billion tobacco users worldwide, with 7.7 million user deaths in 2019 [1]. Se­condhand smoke causes more than 42,000 deaths in the United States annually [2]. Even though smoking rates have declined over the years, smoking continues to be the leading cause of preventable death in the United States [3]. Cigarette smoking costs the healthcare system more than 225 billion dollars per year [4]. Many active smokers do would like to quit smoking and attempt to quit throughout their tobacco use. It may take some up to 30 times to quit smoking [5]. Multiple attempts to quit smoking can be linked to numerous reasons from cravings and withdrawal side effects to lack of support. As practitioners, it is crucial to understand the difficulty of quitting smoking and offer support through nicotine replacement pro­ducts, referrals to support groups or pharmaceuticals as needed. We present a case report of a rare side effect of nicotine withdrawal: hyperactive delirium. While nicotine withdrawal is a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition, hyperactive delirium is not one of the listed known effects. The objective of this case report is to raise healthcare providers’ awareness of one of the more rare side effects of  nicotine withdrawal when admitting smokers to inpatient units or other long-term medical-care stays.

■ Case description

A 61-year-old Caucasian male with a past psychiatric history of major depressive disorder, alcohol-use disorder and tobacco use disorder and pertinent medical history of hypertension and mild intermittent asthma, self-presented to the emergency department with suicidal ideations and alcohol intoxication. The patient reported recent stressors including being fired from his job leading to active suicidal ideations with both intent and plan. The patient’s vital signs including blood pressure and heart rate were within normal limits upon initial evaluation. His mental status exam revealed the patient was oriented to person, place, and time and was otherwise unremarkable except for active suicidal ideation. His blood alcohol level upon admission was 221 mg/dl. The patient required inpatient admission due to being a danger to himself or others and was voluntarily admitted to the dual diagnosis psychiatric unit for active suicidal ideation and alcohol detoxification. Due to the patient’s history of chronic alcohol use disorder and blood alcohol level of 221 mg/dl on admission to the hospital, he was started on an alcohol withdrawal detoxification with a benzodia­zepine taper to avoid potential alcohol withdrawal. He was started on lorazepam 1 mg every four hours, which was decreased to 0.5 mg every four hours after 4 days, and tapered again to 0.25 mg every four hours after another 4 days until discontinued.
On day two of admission, the patient had an unwitnessed fall and his physical examination was unremarkable for any signs of trauma. On general assessment, the patient was oriented only to self and was experiencing visual hallucinations according to nursing staff, resulting in increased agitation and multiple attempts to leave the inpatient hospital unit. On day three of admission, the patient reported visual hallucinations that consisted of a nurse putting pills into his mouth with an ungloved hand behind the nurses’ station. The patient was adamant that this was not a hallucination and that it did in fact happen. The patient continued to request to leave the unit because of the distress caused by his hallucinations. On day four of admission, the patient still reported hallucinations of a nurse putting pills in his mouth without gloves. The patient was increasingly irritable and demanding release home. The patient was oriented to self and place though he stated it was January when it was October. Upon review of records, the patient had remained adherent with the benzodiazepine taper that was started at the time of admission and he was not scoring on the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol, reflecting that he was not showing any signs of symptoms of alcohol withdrawal. Furthermore, the patient denied symptoms of alcohol withdrawal including anxiety, tremors, nausea, vomiting, paroxysmal diaphoresis, restlessness, tactile disturbances, auditory disturbances and headache. His heart rate and blood pressure remained within normal limits throughout his admission.
Due to the patient’s onset of hyperactive deli­rium in the context of the absence of any signs or symptoms of alcohol withdrawal, the treatment team further reviewed the patient’s substance use history. The patient denied any prior history of alcohol detoxification, rehabilitations or history of seizures or delirium tremens with alcohol cessation. When probed by the treatment team about his smoking history, the patient reported a history of smoking three packs of cigarettes per day for the past 20 years. The treatment team subsequently ordered a 21 milligram (mg) nicotine patch which was immediately applied to the patient. The following day, the patient had no recurrence of hallucinations and was still only oriented to self and place. The patient continued to receive a 21 mg nicotine patch daily. Two days after the nicotine patch was applied, the patient continued to deny recurrence of hallucinations, was behaviourally controlled and had a linear thought process. Furthermore, the patient was oriented to self, time, place and situation. He denied suicidal ideation, intent, or plan and was future-oriented. The patient finished alcohol withdrawal detoxification and was no longer a danger to himself or others after stabilisation of medication. The patient was offered rehabilitation but preferred outpatient follow up. The patient was discharged back to his home in a stable condition and a follow up appointment was arranged with an outpatient psychiatric clinic.

■ Commentary

Smoking is the practice of burning tobacco by the user’s choice of medium with the purpose of inhaling the smoke that is tasted and subsequently absorbed into the bloodstream. Tobacco and ciga­rette smoking continue to be a public health issue considering that 23% of the world’s population smokes cigarettes [6]. Given this information, it is important for clinicians to be aware of the possible withdrawal effects of nicotine cessation. Tobacco Use Disorder is a diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), assigned to individuals who are dependent on the drug nicotine due to the use of tobacco products [7]. According to the DSM-5, there are 7 primary symptoms associated with nicotine withdrawal that include “irritability/anger/frustration, anxiety, depressed mood, difficulty concentrating, increased appetite, insomnia, and restlessness” [7]. Nicotine withdrawal can also cause psychiatric symptoms, also known as affective symptoms. Some of these symptoms include anxiety, depression, dysphoria and irritability to name a few. Furthermore, nicotine withdrawal manifests with somatic symptoms which include but are not limited to include tremors, low heart rate and gastrointestinal upset or discomfort [7]. Lastly, nicotine withdrawal cognitive symptoms manifest as difficulty concentrating and impaired memory [8]. However, the acute cessation of nicotine can rarely manifest as hyperactive delirium, such as in this patient’s case.
Hyperactive delirium is a state of increased arousal that can present with symptoms of agitation, restlessness and, at times, aggressiveness [9]. One study set out to assess if there is a risk of developing hyperactive delirium in tobacco users during inpatient hospitalisations secondary to abrupt tobacco and nicotine cessation. The study concluded that patients who underwent sudden cessation of tobacco and nicotine while hospitalised were more likely to exhibit symptoms of hyperactive delirium than hospitalised non-smokers [10]. The study concluded that smoking cessation in tobacco users was an independent risk factor for hyperactive delirium in the inpatient setting [10]. Nicotine withdrawal has been shown to result in a combination of psychiatric, somatic, and/or cognitive symptoms which reflects changes in cholinergic transmission throughout various areas of the brain and anatomical structures [11]. It has been shown that there is down-regulation and desensitisation of nicotinic acetylcholine receptors in the brains of chronic smokers [10]. When a chronic smoker suddenly ceases cigarette smoking, the unoccupied state of nicotinic acetylcholine receptors is what causes withdrawal symptoms [10]. Similarly, delirium also results from changes in cholinergic transmission and deficits while imbalances in dopamine, serotonin, and gamma-aminobutyric acid pathways have also been implicated [10]. Given that the pathophysiology of nicotine withdrawal and delirium have overlapping deficits within similar neurotransmitter symptoms, it is not surprising that sudden nicotine cessation increases risk of hyperactive delirium.
Given that the patient was undergoing detoxification from alcohol with a benzodiazepine taper and was consistently not scoring on the CIWA, his hyperactive delirium was attributed to the abrupt cessation of nicotine withdrawal especially in the context of the patient smoking three packs of cigarettes per day for the past 20 years. Furthermore, the cessation of delirium in this patient after application of a nicotine patch led the treatment team to attributing these symptoms to nicotine withdrawal. Overall, this demonstrates that clinicians who treat nicotine-using patients should be aware of potential nicotine-withdrawal side effects, including the more rare side effect of hyperactive delirium, when admitting patients to inpatient units or any other long term health care stays.

References