Psychiatric management of Patients in intensive care units.

Abstract

INTRODUCTION Since the birth of intensive care medicine in 1953, psychiatrists have played increasingly an important role in providing services to the patients admitted to intensive care unit (ICU). A paper published in JAMA as early as 1965 is one of the first documentations of psychiatric consultation in ICUs.[1] Significance of the topic is underscored by high prevalence of psychiatric disorders in ICUs, which ranges from below 20% to above 60% according to the type of ICU and assessment methodology[2] and includes various organic brain disorders and other psychopathologies. SCOPE The objective of the current guidelines is to provide recommendations to psychiatrists and critical care teams, and the scope includes: Management of psychiatric problems in ICU patients Management of psychiatric emergencies arising out of Suicide attempt Complications related to alcohol and substance use Toxicity/complications related to psychotropic medications Addressing ethical issues, capacity assessment for informed consent for procedures, etc. Sensitivity to stress and burnout issues in ICU team. A general approach of psychiatric consultation in ICU is presented first [Figure 1]. Assessment and management of commonly encountered and important conditions for which psychiatric referrals are made in the ICU are elaborated thereafter.Figure 1: General approach of psychiatric consultation in ICU. ICU – Intensive care unitCALL TO PSYCHIATRIST FROM THE INTENSIVE CARE UNIT – ACCEPTING CALL TO ATTEND INTENSIVE CARE UNIT PATIENT By definition, ICU is the place for treatment of the critically ill who deserve to be attended on priority. Paper/electronic medical record notification is often accompanied by verbal/telephonic notification and serves to communicate acceptance of the call to attend the ICU patient. The degree of urgency to attend the call is generally communicated by the referring ICU team, and depending on the setting, the first responder could either be a psychiatry resident or consultant, and reporting/escalation protocol is expected to be in place in case of residents attending the call. COMMUNICATION WITH REFERRING INTENSIVIST AND GETTING BRIEFING ABOUT THE CASE Communication with the referring intensivist, either during the referral call or at a subsequent opportunity, provides important opportunity to get briefing about the case including the specific reason for referral. Organic brain disorders top the list of referrals followed by suicide attempts and anxiety/depression [Table 1].[3]Table 1: Diagnostic break-up of psychiatric referrals in intensive care unitGATHERING BACKGROUND INFORMATION On entering the ICU, it is prudent to obtain all the relevant information about the case available from different sources, viz., medical records – which contain information such as case history and physical examination notes, chart of vitals, reports of laboratory investigations, medical diagnosis, ongoing treatment and interventions, progress notes, and record of behavioral abnormality. Since patient relatives have limited physical presence in the ICU, nursing staff and resident doctors in the ICU are important source of direct behavioral observation. It is therefore fruitful to spend few minutes interacting with them in addition to reviewing the medical record. Patient’s caregivers are useful source of prior medical and psychiatric history and treatment, events leading to the ICU admission, and course in the ICU including patient’s behavioral response. Importance of gathering detailed background information is highlighted by the fact that ICU patients may not be in a condition to provide much details by themselves. INTERVIEWING INTENSIVE CARE UNIT PATIENT AND CONDUCTING MENTAL STATE EXAMINATION Interviewing ICU patient/conducting mental state examination (MSE) is a skilled task. Psychiatrist needs to be swift in conducting the mental state and other bedside examination without unduly stressing the patient. Availability of rich background information is therefore very helpful. Barriers in conducting interview/MSE may include difficulty in comprehension/difficulty in expression or low level of alertness on account of either medical condition or effect of medication. Initial assessment focuses on making quick judgment about the extent to which verbal assessment can proceed, and careful behavioral observation plays very important role in the overall assessment of clinical condition. ADDITIONAL ASSESSMENT Physical examination ICU patient’s general and systemic physical examination including neurological examination findings recorded in case notes is available to a psychiatrist for review who should however conduct any such examination that may be indicated at the time of attending the call. Additional assessment may include extended neuropsychological assessment or specific scales over and above bedside assessment of MSE. These assessments can be carried out either by the psychiatrist or any other trained personnel. Additional laboratory tests can be ordered to consolidate the clinical impression and to aid the management and may include biochemical tests (such as drug levels), electrophysiological tests such as electroencephalogram, or brain scan such as magnetic resonance imaging. DIAGNOSTIC FORMULATION Diagnostic formulation includes syndromal diagnosis and ascertainment of causality [Figure 2]. Formal classification such as the International Classification of Diseases (ICD) system (current 10th version, and soon to be introduced 11th version) provides clinical descriptions and diagnostic guidelines.Figure 2: Decision process leading to diagnostic formulationThe psychiatric syndrome/disorder may either be linked to the medical illness or its treatment, or attributable to the stress of illness and environment, or a primary psychiatric disorder including alcohol and substance use. ICU stay itself could be very stressful. Patients in the ICU experience physical and psychological stress related to the serious and often life-threatening illness, which is compounded by the aspects of ICU environment such as frequent movement of staff, noise of machines, masking of zeitgebers, restrictions on patients regarding mobility and communication, and being witness to adverse outcome of other patients; weakness, fatigue, and cognitive impairment may have additive effect. MANAGEMENT PLAN AND PRESCRIPTION, WITH DUE CONSIDERATION OF ETHICAL ASPECTS Very often, quick mitigation of the index behavioral disturbance is expected from the psychiatric referral. However, choice of pharmacotherapy including the agent, dose, and route of administration warrants careful consideration of the following given in Box 1.Box 1: Considerations in choice of pharmacotherapyA concise note of psychiatric consultation is expected which is able to communicate the inference and management plan with clarity to nonpsychiatrists of ICU team. Psychological intervention, especially supportive counseling, as permitted by patient’s present state, is helpful in alleviating fear, anxiety, and stress associated with the illness and with ICU milieu.[4] Briefing ICU staffs about the anticipated response of psychiatric intervention, watching out for any adverse response, and prompt reporting of the same are important steps to ensure quality care. If any PRN prescription is made, it is best to specify the situation which should trigger its use. Briefing patient relatives about the psychiatric intervention being prescribed is equally important, especially considering the fact that many ICU patients may be in a vulnerable condition unable to consent in true sense. However, due care should be taken to protect confidentiality of patient narrative, particularly when the patient has indicated so, as is often the case in suicide attempt. Being the place of treatment of critically and terminally ill patients, ICU is also the setting of several ethical dilemmas and considerations, which may range from physical procedures, such as application of restraints, to psychological procedures such as breaking bad news, preparation for end-of-life situation and helping relatives make difficult decisions such as taking patients off life support, and facilitation of advance directives. Family satisfaction is related to clinician communication.[5] It could also be the setting to detect foul play and protect the patient and to encourage altruistic actions such as organ donation. COVID-19 situation has generated debate about the role and limitations of teleconsultation for ICU patients. It needs to be appreciated that family members may also find the situation challenging and experience depression, anxiety, or anticipatory grief and deserve to be supported as per the need. Prevalence of posttraumatic stress disorder (PTSD) risk is 16%–21% during 6 months postdischarge,[67] and relatives can be made aware about availability of psychiatric help should they need it. FOLLOW-UP No quality management plan is complete without follow-up. The frequency of follow-up is often mutually worked out between the intensivist and the psychiatrist and may include postdischarge visits for continuation of psychiatric intervention. The point prevalence of PTSD symptoms in the ICU patients ranged from 15% to 20% after 3–12 months of discharge as shown by recent meta-analysis of 48 studies,[8] and the psychiatrist should be vigilant for timely management of the same. Cognitive dysfunction, particularly after delirium, is also a common sequel (17%–78%) which may persist for up to several years but tends to improve over time,[9] and it is prudent to screen as a routine on the follow-up visit. Depending on the nature of the case attended in the ICU (e.g., suicide attempt or alcohol withdrawal) and as per the discretion of the psychiatrist, optional sharing of telecontact may be helpful for prompt cognizance of any problem postdischarge pending the scheduled follow-up. ASSESSMENT AND MANAGEMENT OF COMMON AND IMPORTANT PSYCHIATRIC CONDITIONS IN INTENSIVE CARE UNIT Delirium Delirium is the most common organic/neuropsychiatric disorder caused by transient disruption of brain neuronal activity, which is secondary to systemic disturbances. Delirium risk factors include older age, dementia, mechanical ventilation, metabolic acidosis, emergency surgery or trauma, hypertension, APACHE II score, and coma; multiple organ failure poses moderate risk. The incidence of delirium in a systematic review of 42 studies on 16,595 patients was found to be 31.8% in critically ill patients and even higher in ICU setting ranging from 60% to 87% in medical ICU and up to 89% in survivors of stupor or coma. The incidence of common surgical condition such as hip fracture is 34%–92%.[10] However, it remains underdiagnosed and under-referred, possibly due to difficulty in recognition by the ICU staff at the extreme of symptom presentation. An Indian study found that the prevalence rate in medical/surgical ICU was 68.2%; however, the referral rate to psychiatric team was 1.7%.[11] Delirium is associated with increased mortality and morbidity, increased incidence of iatrogenic complications, prolonged hospital stay, poor functional and cognitive recovery, and decreased quality of life in addition to increased cost of care and burden to caregivers. Recognizing its significance, Clinical Practice Guidelines for Management in Elderly was brought out by the Indian Psychiatric Society (IPS) in 2018,[12] which provide details of various aspects of management. A brief overview and update is provided for ready reference and to supplement these guidelines. Clinical presentation Delirium presents with acute onset of fluctuating cognitive impairment (disorientation, memory disturbance) and disturbance of consciousness/awareness with a reduced ability to attend and shift attention, which is frequently associated with perceptual abnormalities, sleep–wake rhythm dysregulation, disorganized thought process, emotional dysregulation, and abnormal psychomotor activity. A prodromal phase consisting of restlessness, sleep disturbance, anxiety, and irritability may precede few hours or days. Following delirium phenotypes are recognized:[13] Subsyndromal type Hypoactive delirium (extreme-catatonic subtype) Hyperactive delirium (extreme-excited subtype) Mixed type The protracted or persistent type. Hypoactive type is most common (65%) and often under-recognized. Assessment and management of delirium Delirium assessment and management: Five Steps: Figure 3.Figure 3: Delirium assessment and management: Five stepsManagement of known risk factors of the delirium While old age, medical illness, cognitive impairment, and pre-existing brain disorders are nonmodifiable risk factors, whereas several other risk factors could be modifiable, viz., various medicines, especially opioid and GABA-ergic medicine, medications with anticholinergic effects, prolonged and/or uninterrupted sedation, restricted mobility, acute intoxication and withdrawal states, nutritional deficiencies, metabolic disturbances, water and electrolyte imbalances, endocrinopathies especially hypo or hypercortisolemia, poor oxygenation states (viz., hypoperfusion, hypoxemia, anemia), sleep–wake cycle disruption, and uncontrolled pain [Table 2].Table 2: Risk factors for deliriumDelirium prevention strategies Considering the negative consequences of delirium, its prevention is of utmost importance. Delirium is considered as one of the six most common preventable conditions observed among hospitalized elderly patients.[13] Delirium prevention strategies may be pharmacologic and nonpharmacologic. Nonpharmacologic strategies are considered superior and include: Providing orientation to time, place, person, and situation Involving family in patient care. Sensory aids such as hearing aids and correcting glasses Cognitive stimulation and memory clues Mobilizing patient early Noise and light reduction to aid night-time sleep. Effectiveness of nonpharmacologic strategies was demonstrated by the Hospital Elder Life Program in which hip fracture repair subjects had significant decrease in onset of delirium (32% in the intervention group compared to 50% in the usual care group). A recent meta-analysis of 14 studies of multicomponent nonpharmacological interventions showed reduced incidence of delirium and prevented falls, that is, how decreased length of hospital stay. Pharmacologic prevention strategy Pharmacologic prevention strategy includes: Minimal use of the pharmacologic agents that may contribute or worsen delirium Judicious use of sedation Adequate treatment of pain. Potentially high deliriogenic or anticholinergic drugs are to be best avoided in the treatment of delirium, which include GABA-ergic agents for sedation and control of agitation with the exception of cases of central nervous system-depressant withdrawal, viz., alcohol, benzodiazepines, and barbiturates, or when more appropriate agents have failed. Use of opioid agents should also be avoided and opioid-sparing strategies such as prescription of parecoxib could help in prevention of postoperative delirium. A meta-analysis revealed that compared to the conventional GABA-ergic agents such as midazolam or propofol for sedation, use of dexmedetomidine was associated with less delirium. Indian Society of Critical Care Medicine survey however found that nearly, all the respondents use midazolam for sedation (95%) followed by propofol (68%) and dexmedetomidine (60%);[15] more awareness could help improve this trend. REDUCE trial that evaluated the delirium prevention with haloperidol did not show any benefit.[10] Statin therapy meta-analysis also did not support any beneficial action. Perioperative use of prophylactic antipsychotics was found to be useful in reducing the risk of postoperative delirium. A meta-analysis of 38 studies supported role of dexmedetomidine, antipsychotics, and multicomponent interventions in preventing postoperative delirium.[13] Medications which strengthen circadian rhythm such as suvorexant (potent orexin antagonist) and ramelteon (melatonin agonist) were helpful to lower risk of delirium in the elderly patients;[10] results from large randomized controlled trial on prophylactic melatonin (Pro-MEDIC trial) are awaited. Acetyl cholinesterase inhibitors have protective role in patients with dementia. Society of Critical Care Medicine has developed a group of interventions called the ABCDEF bundle, which incorporate various prevention strategies listed above. The bundle can help decrease delirium.[14] Its A to F ingredients are: Assessment, prevention, and management of pain Spontaneous awakening trial Spontaneous breathing trial Choice of sedative agent (proper choice) Delirium monitoring and management Early mobilization and physical exercise Family involvement and empowerment A recent meta-analysis that included 26,384 patients from 11 studies supported effectiveness of bundle interventions in reducing length of hospital stay, proportion of days with coma, and 28-day mortality, although the prevalence and duration of delirium were not altered significantly.[15] Surveillance and accurate diagnosis Surveillance is critical to timely detection of delirium. For this, the standardized surveillance tools such as Confusion Assessment Method (CAM), Intensive Care Delirium Screening Checklist, Stanford Proxy Test for Delirium (S-PTD), and Rapid Assessment Test for Delirium (4AT) and diagnostic tools such as CAM for ICU or Memorial Delirium Assessment Scale are helpful. A multinational survey from 47 countries revealed that delirium monitoring is carried out in 70% of the ICUs, but only 42% used a validated screening tool.[10] Indian Society of Critical Care Medicine survey reported that only 35% of the intensivists were assessing delirium.[16] These surveys underscore the need for training medical personnel at each levels regarding the prevalence and symptoms of delirium, particularly awareness about its subsyndromal form and use of appropriate screening tools. 4AT and S-PTD are newer tools that have 90% and 79% sensitivity and 84% and 90.8% specificity, respectively. Other useful tools are the Richmond Agitation-Sedation Scale, the Sedation-Agitation Scale, and Neelon and Champagne Confusion Scale for nurses. ICD-10 and DSM-5 are the diagnostic gold standards for delirium. Important points in clinical workup of delirium include: History – Present and past medical history, risk and precipitating factors including medication history, drug and alcohol history, sudden onset (within hours or days) with a fluctuating course Physical examination – Careful note of vitals, oxygen saturation, examination of skin for “tracks” (intravenous drug use), signs of infection, and any source of pain Neurological examination – Re-emergence of pathologic primitive signs such as glabellar tap reflex, rooting reflex, snout reflex, suck reflex, grasp reflex, palmomental reflex, and Babinski sign MSE (core domains of delirium) Psychomotor dysregulation – Agitation (floccillation or carphologia), retardation, or mixed presentation Cognitive deficits – Clouding of consciousness, inattention, i.e., impaired ability to direct, sustain and shift both visual and auditory attention, disorientation of time, place, and person, and memory impairment Language impairments (rambling, incoherent, or illogical speech) Disordered thinking – Delusional thinking, abstract thinking, and comprehension Executive dysfunction Altered perceptions (illusions and hallucinations) Circadian rhythm dysregulation: “Sundowning” sleep–wake cycle disturbances with nocturnal worsening Emotional dysregulation – Affective lability characterized by anxiety, perplexity, fear, sadness, irritability, apathy, anger, or euphoria Investigations – Various indicated hematologic, biochemical, electrophysiological, and imaging tests are important to uncover the etiology (For details please refer IPS Practice Guidelines for Delirium). Management of psychiatric and behavioral manifestations of delirium Pharmacologic treatment is effective for all types of delirium. Antipsychotics are useful in many ways to control agitation and psychosis, to normalize short-term memory and primitive reflexes, and to protect neurons against hypoxic stress and injury.[13] A systematic review of 28 studies revealed that clinical improvement is seen in about 75% of patients receiving short-term treatment with low-dose antipsychotics. The treatment response rates observed were consistent across different patient groups and treatment settings, and there were no major differences in the response rates between the clinical subtypes of delirium. No significant difference was observed between efficacy of haloperidol and atypical agents, and the dose of antipsychotics is dependent upon the type of delirium being treated. In hyperactive delirium, moderate dose of haloperidol is considered to be the treatment of choice subject to the patient’s cardiac condition and absence of significant electrolyte abnormalities.[13] In a study of advanced cancer patients with agitated delirium, addition of lorazepam to haloperidol resulted in a significantly greater reduction in agitation at 8 h.[17] When use of haloperidol is not considered desirable or is contraindicated, atypical antipsychotics should be used. More data exist for risperidone and quetiapine, whereas data are limited for olanzapine, aripiprazole, lurasidone, and paliperidone. Sedative potential and half-life are important considerations in choosing any one of them. Clozapine and ziprasidone are best avoided. It is safe practice before prescribing antipsychotic agents:[13] Obtaining 12-lead electrocardiogram and measuring QTc Checking electrolytes and correction of potassium (K) and magnesium (Mg) if required Reviewing the list of medication to identify agents with propensity to prolong QTc and avoiding/replacing such medicines or inhibitors of CPY3A4 Discontinuing antipsychotic use if QTc increases to greater than 25% of baseline value or is greater than 500 ms Evidence about the utility of other pharmacotherapeutic agents in the management of delirium[14] Acetyl cholinesterase inhibitor (rivastigmine, donepezil) in patients of delirium superimposed on known cognitive deficits or a history of recurrent delirium is not encouraging. One study suggested an increased mortality associated with their use, warranting caution. Physostigmine is used as the first-line treatment for central anticholinergic syndrome and antimuscarinic delirium Melatonin or melatonin agonist ramelteon is helpful in promoting sleep in all types of delirium Alpha-2 agonists such as dexmedetomidine and clonidine have a role in protecting against neuronal injury and worsening of delirium associated with acute norepinephrine release secondary to hypoxia or ischemia. Primary sedative agents can be changed from GABA-ergic agents such as propofol or midazolam to dexmedetomidine. Clonidine is also other useful alternative, especially to wean patients off dexmedetomidine Anticonvulsant and other agents with glutamate antagonism or calcium channel modulation such as valproic acid find utility in the management of agitated delirious patients who are poor responders or cannot tolerate antipsychotic treatment; however, the data are limited. Same is true of carbamazepine and gabapentin. Amantadine and memantine could be useful in cases of traumatic brain injury (TBI) and cerebrovascular accident (CVA). Pharmacologic treatment of hypoactive delirium involves very-low-dose haloperidol given just before sun down or low dose of risperidone or aripiprazole. In case of marked psychomotor activity retardation or presence of features of catatonia in patients without psychosis, use of psychostimulants such as modafinil, methylphenidate, or dextroamphetamine may be considered. Amantadine, memantine, or bromocriptine may be of help in the management of severe psychomotor retardation in cases of TBI and CVA. Nonpharmacologic treatment of all types of delirium is similar to the nonpharmacologic strategies of prevention of delirium described previously. Identification of etiology and treatment of underlying medical condition(s) Definitive treatment of delirium involves accurate identification of the underlying cause and its timely treatment, which is entrusted to ICU consultee team of intensivist and physician/surgeon. Quick and safe correction of malnutrition, dehydration, and electrolyte abnormalities is part of general management, and so also, minimization of use of medicines may contribute to triggering or worsening delirium, whereas specific management is dependent upon the underlying cause(s). Clinicians find the acronym “I WATCH DEATH” useful as a checklist to investigate the underlying cause[1819] [Table 3].Table 3: Delirium etiology[19] Additional points about management of delirium linked to alcohol withdrawal, a common condition in clinical practice, find mentioned in a later section Organic brain syndromes linked specifically to adverse reaction/toxicity of psychotropic medication, viz., neuroleptic malignant syndrome (NMS), serotonergic syndrome (SS), and toxicity of mood stabilizer, specifically lithium overlaps with delirium. Although their occurrence is rare, these are potentially serious conditions and it is important that psychiatrists are aware for prompt recognition and early institution of management. Neuroleptic malignant syndrome NMS is a life-threatening condition related to adverse reaction to dopamine antagonists or to rapid withdrawal of dopaminergic medications [Table 4] presenting within hours or days as syndrome of altered mental state, muscle rigidity, fever, and autonomic dysregulation with laboratory evidence of muscle injury (e.g., elevated CPK-10 fold rise).[2021] Risk factors include presence of dehydration, physical exhaustion, exposure to heat, hyponatremia, iron deficiency, malnutrition, alcohol, trauma, thyrotoxicosis, psychoactive substances, and presence of a structural or functional brain disorder. Mortality rate seen is 5%–20% and average period of recovery is 7–11 days.IPS Clinical Practice Guidelines for Management of Schizophrenia also touches upon factors associated with risk of NMS.[22] Table 4: Medications associated with causation of neuroleptic malignant syndromeManagement of neuroleptic malignant syndrome Being a rare complication, management insight is based on case series and includes Stopping all dopamine blockers Starting dopamine agonist medicines if NMS is caused by stopping it. Supportive care Adequate hydration, correction of electrolyte imbalance, external cooling (ice packs in axilla, cooling blankets), gastric lavage of ice water, and use of paracetamol Lorazepam is useful for agitation and clonidine may be used for autonomic instability (hypertension) Preventive measures for deep vein thrombosis. Specific measures Bromocriptine: starting dose is 2.5 mg 2 or 3 times daily, increased by 2.5 mg every 24 h until a response or until reaching a maximum dose of 45 mg/day. The dose is maintained up to 10 days in case of oral antipsychotics and 2–3 weeks in case of depot preparations Other drugs such as amantadine hydrochloride, levodopa, apomorphine, and dantrolene can also be tried. Role of ECT is controversial and recommended where nonpharmacological treatment is required or where drug treatment fails. Restarting antipsychotics Since recurrence may happen after restarting high-potency antipsychotic or early after recovery, it is prudent to wait for at least 2 weeks for oral antipsychotics or 6 weeks for depot antipsychotics; low-potency antipsychotics are preferred, starting with low dose and up-titration in slow and careful manner. Serotonin syndrome SS (serotonin toxicity) is a life-threatening condition resulting from therapeutic drug use, intentional self-overdosing, or an inadvertent interaction between the drugs. Selective serotonin reuptake inhibitors (SSRIs) are one among the most common in overdose and serotonin toxicity occurs in 15% of SSRI-overdose patients.[232526] Severe serotonin toxicity is a medical emergency usually complicated by rhabdomyolysis, hyperthermia, disseminated intravascular coagulation, and adult respiratory distress syndrome. Onset is generally acute <12–24 h with rapid progression. Resolution can be expected within 24 h if uncomplicated, and mortality is low (<1%) when proper treatment is given. Research groups of Sternbach, Hunter, Radomski and colleagues, and Dounkeley have proposed the diagnostic criteria. Mild cases present with tachycardia, mild hypertension, mydriasis, diaphoresis, shivering, tremor, myoclonus, and hyperreflexia without fever. Hyperthermia (40.8°C), hyperactive bowel sounds, horizontal ocular clonus, mild agitation, hypervigilance, and pressured speech are seen in moderate cases. Severe cases include hyperthermia (greater than 41.18°C), dramatic swings in pulse rate and blood pressure (autonomic dysfunction), delirium, and muscle rigidity. Complications such as myoglobinuria, seizures, rhabdomyolysis, metabolic acidosis, renal failure, acute respiratory distress syndrome, and respiratory failure may be seen in some cases and rarely diffuse intravascular clotting, coma, and death. Table 5 depicts the medication groups and different combinations of drug can cause SS.Table 5: Medications associated with causation of serotonin syndromeManagement of serotonin syndrome Treatment is mainly supportive. All serotonergic medication is to be stopped first. Supportive care Adequate hydration, correction of electrolyte imbalance, external cooling (ice packs in axilla, cooling blankets), and prescription of benzodiazepine for agitation In case of severe agitation and hyperthermia, 5HT-antagonist cyproheptadine may be used in an initial dose of 12 mg with the addition of 2 mg every 2 h if symptoms persist Severe hypertension/tachycardia