Deliriumtremens (DT) is the severest form of alcohol withdrawal and is recorded in approximately 5% to 24% of patients [1-5]. Over the last few decades, the mortality rate for patients with DT has fallen from 35% to 2%, and this has been largely attributed to improved diagnostic and pharmacological measures [2,6-11]. Several studies have identified risk factors for the occurrence of DT [5,12-18], but there has been little research into the risk factors for mortality among patients with DT [3,6,10,18,19]. The factors that predict a fatal outcome in patients with DT remain unclear, and DT is still categorized as an
Conclusions: The prevalence of alcohol dependence in hospitalized patients is substantial. Although our patient was being treated with the standard protocols for alcohol withdrawal, he rapidly developed deliriumtremens, which led to an acute inferior ST-elevation myocardial infarction in the setting of nonoccluded coronary vessels. This case report adds to the sparse literature documenting acute coronary events in the setting of alcohol withdrawal and suggests that our patient ’ s ST-elevation myocardial infarction is not fully explained by the current coronary vasospasm hypothesis, but rather was in part the result of direct catecholamine-associated myocardial injury. Further research should be conducted on prophylactic agents such as β -blockers and calcium channel blockers.
5 Schuckit MA, Tipp JE, Reich T, Hesselbrock VM, Bucholz KK. The histories of withdrawal convulsions and deliriumtremens in 1648 alcohol dependent subjects. Addiction 1995;90:1335–47. 6 Hawley RJ, Major LF, Schulman EA, Linnoila M. Cere- brospinal fluid 3-methoxy-4-hydroxyphenylglycol and norepi- nephrine levels in alcohol withdrawal. Correlations with clini- cal signs. Arch Gen Psychiatry 1985;42:1056–62.
tor leads to anxiolysis, sedation and impaired motor co-
ordination. Chronic alcohol ingestion induces tolerance through reduction of GABA A receptor function as well as
up-regulation of NMDA receptors, which results in a com- pensatory increase in excitatory neurotransmission. Lack of inhibition by alcohol due to reduced or discontinued alcohol use leads to excessive central nervous system ex- citation (symptoms of withdrawal) . With drawal symp- toms arise within hours to days of alcohol abstinence and range in degree from sympathetic hyperactivity, nausea or vomiting to hallucinations and withdrawal seizures and, most severely, deliriumtremens (DT). Clinically, DT presents as disorientation, agitation, hallucinations, tremors, diaphoresis, tachycardia, hypertension and pyr- exia (i.e. symptoms corresponding to hyperactive delir- ium). DT occurs in 5-20% of alcohol withdra wals, typically 1-5 days after alcohol abstinence, and DT carries a mor- tality rate of up to 25% although treatment can reduce this to 0-1% . Mortality is caused by complications to the clinical manifestations of DT, i.e. myocardial infarc- tion due to autonomic hyperactivity . Delirium usually lasts from three to five days, up to two weeks, though rare cases of even longer DT periods do exist .
Clinicians differ in how well they adhere to these criteria, so it is difficult to determine the preva- lence of withdrawal delirium, and rates depend on whether persons with this condition were treated as outpatients, as general medical or psy- chiatric inpatients, or as patients in an intensive care unit (ICU). Most studies estimate that 3 to 5% of patients who are hospitalized for alcohol withdrawal meet the criteria for withdrawal de- lirium. 7,10,11 Retrospective chart reviews based on
adrenergic antagonists, clonidine, and neuroleptics were found to ameliorate withdrawal severity and can be considered useful adjuncts. Phenothiazines ameliorate withdrawal but are less effective than benzodiazepines in reducing delirium or seizures. The following conclusions can be made based on a limited number of controlled clinical trials; (1) agents with rapid onset control agitation more quickly; (2) agents with a long duration of action provide a smooth treatment course with less break-
One vehicle for increasing access of delirium practice tools at the point of care is E-health . The World Health organization defines E-health as the process in which health resources and healthcare are being com- municated and transferred by electronic media . Over the last decade, there has been a massive advance in E- health, which has led to the creation of multiple online learning platforms for clinicians and allied healthcare professionals to stay abreast of the latest treatment algo- rithms and guidelines. Since 2010, there has been an ac- companying advancement in M-health as well, which refers to the usage of mobile and smartphone technolo- gies in healthcare. With the growth and advancement in M-health, smartphone are being increasingly used med- ical disciplines , surgical disciplines  and psychiatry . It is thus not surprising that with the introduction of smartphones, healthcare professionals are beginning to turn to smartphone applications to aid them in clinical assessment and management . Prior studies have highlighted the utility of smartphone applications as quick and interactive platforms that are time saving and allow for increased confidence and accuracy, as well as error reduction in the detection and management of various clinical conditions . By providing instant ac- cess to medical information, it is postulated that applica- tions not only improve communication amongst staff, but help healthcare professionals in decision-making. The cumulative effect of these factors would be the
Delirium screening should be preferably performed by nurses because they have frequent contact with the pa- tient throughout the day, and could therefore easily ob- serve changes in the patient ’s attention and awareness over time, which is one of the main criteria for delirium according to the DSM 5 criteria [ 21 ]. The Delirium Ob- servation Scale (DOS) appears to be the most suitable nurse-rated screening instrument for patients in general medical and surgical wards with a strong foundation in the DSM-IV criteria and good psychometric properties [ 3 , 22 ]. It can be assessed by nurses without specific training, and is experienced as user-friendly. A previous, small study by Detroyer et al suggests good sensitivity and specificity of the DOS in a palliative care population [ 23 ]. The aim of our study is to evaluate the diagnostic accuracy of the DOS as screening instrument for hospi- talized patients diagnosed with advanced cancer.
Given the fact that the development of delirium can be predicted only 24 h after ICU admission, and the clear relation between time to treatment with haloperidol and the duration of delirium , initiation of prophylaxis as early as possible is warranted. Based on our historical data, the median predicted risk of delirium is approxi- mately 35% in patients with an expected stay on the ICU of over one day; this is considered a high risk for delirium development. A clinical estimation of an ICU LOS >1 day is possible within the first few hours after ICU admission. Previous studies that included patients using similar criterion of an expected ICU LOS were found feas- ible [20,21]. Therefore, the clinical estimation by the attend- ing ICU-physician of an ICU LOS >1 day will be used as an inclusion criterion for this study, in which the prediction to develop delirium (using the PRE-DELIRIC model ) will be used to facilitate post-hoc analyses to investigate which patients benefit most from prophylactic therapy. By using the PRE-DELIRIC score as an a priori determined post-hoc analysis, we will learn if the putative beneficial effect of haloperidol is related to the risk to develop delirium, or comparable in all patients, independent of the baseline risk to develop delirium. In addition, it will facilitate the deter- mination of a cut-off level for the PRE-DELIRIC score.
Astrocytes, which express the IL-1 β receptor, are involved in neuro- in ﬂ ammation, when they multiply and produce in ﬂ ammatory interme- diates . Van Munster et al. have found increased GFAP staining in hippocampal sections from patients who died with delirium , but here we found no signi ﬁ cant difference in CSF levels. CSF levels of GFAP were negatively correlated with CSF IL-1ra; if the presence of increased IL-1ra is a neuroprotective response, greater IL-1ra produc- tion may lead to less astrocyte activation. The levels we detected in our elderly cohort were similar to those found in younger patients with MS  and older patients with movement disorders , and lower than that seen in traumatic brain injury , and stroke . GFAP is a structural protein of the cytoskeleton of ﬁ brillary astrocytes, and its release into CSF is usually associated with acute CNS injury or astrogliosis [68,71].
to decrease the incidence of postoperative delirium and haloperidol has been shown to decrease the severity and duration of postoperative delirium. Even though one study in the literature review was inconclusive, antipsychotics show an overall positive effect on postoperative
delirium. Antipsychotics are commonly used in practice. However, they may cause serious side effects such as sedation, extrapyramidal reactions, seizures, neuroleptic malignant syndrome, QT prolongation, and the development of type 2 diabetes (Gutierrez, 2008). More research should be conducted, but overall it is recommended that antipsychotics be used with caution and only when the benefits outweigh the risks. Clonidine, an alpha-2 adrenergic agonist, has also been shown to reduce the severity of delirium, improve respiratory function, shorten ventilator weaning time, and shorten ICU length of stay. This is not surprising considering that it is in the same drug class as dexmedetomidine. More research should be conducted, but clonidine seems to have great potential to reduce postoperative delirium.
Screening instruments for delirium in the ED have had remarkable success. There
are many delirium screening instruments available requiring little time and no special
training, however, these are not well-known, nor are they commonly used. Apold (2018)
found the Confusion Assessment Method was the most common, but required specific
display signs of delirium at night. However this was not possible due to limitations in resources. Furthermore a certain number of participants may not score positively on the CAM-ICU, as it is feasible that the cut off points for a positive diagnosis may have been set too high, making it harder to reach diagnostically. Despite not scoring highly positive on the CAM-ICU, these participants still exhibited signs of delirium and were included in the incidence figures. This is classed as sub-syndromal delirium, which was discussed previously in Chapter one (Section 1.1.2). In this study this was true for 20 patients who exhibited signs of sub-syndromal delirium, accounting for less than 7% of the study sample. The DRS-R98 was completed for all participants as it relied on the information from the medical notes, staff on the stroke unit and the researcher’s own observations. According to the literature, patients with the hypoactive type of delirium have the worst prognosis and are missed in about 75% of cases  , as discussed in Chapter one. This is often due to similar presentations of hypoactive delirium, dementia and depression. In some cases delirium can be found super imposed on pre-existing dementia  , making it difficult to make a diagnosis. In addition to this, the literature suggests that people with dementia may be much more susceptible to developing delirium, as previously discussed in Chapter one. Multiple diagnoses do exist in clinical practice but the primary focus of this study was to determine the level of delirium present in the study population. Only one researcher was used to administer the assessment tools which ensured that the assessments were conducted in exactly in the same manner. All four parts of the CAM-ICU were performed on all patients regardless of delirium diagnosis, at the same time points in the study in order to avoid bias. The assessment tools were well tolerated by the patients in this study.
• should be considered a diagnosis of exclusion after all other causes have been thoroughly investigated
• Many primary prevention and treatment strategies for delirium involve relatively simple methods to address the aspects of the inpatient setting that are most confusing.
This study protocol is in accordance with the CONSORT guidelines concerning randomized controlled trials .
Design and setting
A prospective, multicenter, three-armed, permuted block- randomized, double-blind, placebo-controlled, prophylactic intervention study will be conducted in critically ill patients with a high risk of delirium development. All participating sites are members of the Dutch Intensive Care Unit Delirium Consortium facilitating the collaboration related to delirium research in the ICU. In all centers, patients are screened for delirium using the validated Dutch translation of the Confusion Assessment Method-Intensive Care Unit (CAM-ICU) [27-29] by well-trained ICU nurses, at least two times a day and more often if indicated (during periods of fluctuating symptoms or levels of sedation). Before initiation of the study, ICU nurses will receive additional information concerning the CAM-ICU on top of their in-house CAM-ICU training. Furthermore, during the study, inter-rater reliability measurements of the CAM-ICU and the Richmond Agitation Sedation Score (RASS), as part of the CAM-ICU, will be performed in order to check the quality of the assessments, and if necessary, additional training will be provided.
Results: The sample consisted of 140 consecutive delirious patients with a mean age of 68.21±12.07 years. Delirium was diagnosed in 140 of 5,642 patients (2.48%) admitted in CICUS in the last 5 years. The median duration of delirium was 48 hours with a range of 12–240 hours. Statistical analysis showed that hyperactive subtype of delirium and treat- ment with antipsychotics were associated with prolonged delirium duration (hyperactive 76.15±40.53 hours, hypoactive 54.46±28.44 hours, mixed 61.22±37.86 hours; Kruskal–Wallis test: 8.022; P0.05). The duration of delirium was significantly correlated also with blood potassium levels (Pearson’s r=0.2189, P0.05), hypotension (hypotension 40.41±30.23 hours versus normotension 70.47±54.98 hours; Mann–Whitney U=1,512; P0.05), administra- tion of antipsychotics compared to other drugs (antipsychotics 72.83±40.6, benzodiazepines 42.00±20.78, others drugs, mostly piracetam 46.96±18.42 hours; Kruskal–Wallis test: 17.39, P0.0005), and history of alcohol abuse (with a history of abuse 73.63±45.20 hours, without a history of abuse 59.54±30.61 hours; Mann–Whitney U=1,840; P0.05). One patient had suffered from complicated postoperative hypostatic pneumonia and died due to respiratory failure (patient with hypoactive subtype). According to the backward stepwise multiple regres- sion, the best significant predictors of duration of the delirium were the hypotension, type of psychopharmacs, type of delirium, the daily dose of opioids, a combination of psychopharmacs, history of alcohol abuse, plasma level of potassium, anemia, hyperpyrexia, and plasma level of albumin, reaching statistical significance (analysis of variance: F=5.205; df=24; P0.005; adjusted r 2 =0.637).
Methods We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100β, and cortisol were measured during each data acquisition. Results Data from 16 patients, of whom 12 had sepsis- associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV,
The term sepsis-associated encephalopathy (SAE) has been applied to animal models, postmortem studies in patients, and severe cases of sepsis. SAE is considered to include all types of brain dysfunction, including delirium, coma, seizure, and focal neurological signs. Clinical data for sepsis-associated delirium (SAD) have been accumulating since the establishment of definitions of coma or delirium and the introduction of validated screening tools. Some preliminary studies have examined the etiology of SAD. Neuroinflammation, abnormal cerebral perfusion, and neurotransmitter imbalances are the main mechanisms underlying the development of SAD. However, there are still no specific diagnostic blood, electrophysiological, or imaging tests or treatments specific for SAD. The duration of delirium in intensive care patients is associated with long-term functional disability and cognitive impairment, although this syndrome usually reverses after the successful treatment of sepsis. Once the respiratory and hemodynamic states are stabilized, patients with severe sepsis or septic shock should receive rehabilitation as soon as possible because early initiation of rehabilitation can reduce the duration of delirium. We expect to see further pathophysiological data and the development of novel treatments for SAD now that reliable and consistent definitions of SAD have been established.