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Correlation of haloperidol levels in blood and cerebrospinal fluid: A pharmacokinetic study
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9th congress of the EUGMS / European Geriatric Medicine 4 (2013) S142–S216
P513
Pressure ulcer treatment in the hospitalized patient – eHealth as a treatment strategy F. Vânia , M. Joana , S. Susana , M.P. Ana , P. Vítor C.H.U.C., Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal Introduction.– Costs associated with pressure ulcer treatment is high. Although strategies for prevention prove to be more costeffective, literature reviews demonstrate that approximately 5% of patients admitted develop pressure ulcers. Associated to this fact, is the number of people that already present pressure ulcers at the time of admission. Implementation of guidelines are very difficult. As such, if used correctly and as a decision-making support system, eHealth can improve knowledge and, consequently, improve patient care. Objective.– Improve treatment of pressure ulcers through an interactive digital board. Methods.–An interactive digital board was constructed using a decision-making algorithm based on NPUAP© guidelines and TIME algorithm. The algorithm was activated by filling the fields regarding PUSH-II assessment of the wound with two extra fields: odor and infection. After filling all the fields, the recommended treatment was shown. Data for time used for the wound care, materials used and total cost, were also assessed. Results.– In a total of 52 pressure ulcers, high rates of wound healing (56.7–100.0%) were observed though the monthly assessment, with an average cost of 2.51 D /category I, 5.39 D /category II, 6.14 D /category III and 6.21 D /category IV. PUSH-II scores showed overall improvement with the decrease of scores compared to the initial episode. Conclusions.– According to the results, the interactive digital board proves to be a good strategy for the implementation of changes in practice and introduction of guidelines. http://dx.doi.org/10.1016/j.eurger.2013.07.581 P514
Association of selected anti-psychotic agents with all-cause mortality in elderly individuals: A Danish Nationwide Cohort Study M. Sahlberg a , E. Holm b , T.S. Høj Jørgensen b , A. Højmann c , G.H. Gislason d , C. Torp-Pedersen e , C. Andersson d a Department of Geriatric Medicine, Aalborg University Hospital, Aalborg, Denmark b Department of Geriatric Medicine, Nykøbing-Falster Hospital, Nykøbing, Denmark c Department of Geriatric Medicine, Slagelse Hospital, Slagelse, Denmark d Department of Cardiology, Gentofte Hospital, Hellerup, Denmark e Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark Introduction.– In recent years data from observational studies have raised concerns about the safety of treatment with antipsychotic agents (APS) in elderly patients with dementia, but this area is still insufficiently investigated. We studied the outcomes associated with individual APS in elderly individuals using nationwide Danish data. Methods.– We included all individuals in Denmark aged 70 years or older between 1997 and 2009 who had not used APS prior to study baseline. Exposure to APS was assessed by identifying claimed prescriptions from pharmacies. Adjusted relative risks (RR) associated with exposure to APS were calculated by time-dependent Poisson regression models.
Results.– We included 1,235,869 individuals: 100,140 (8,1%) used APS at some point. For all agents, we found a highly increased RR of mortality during the first month after initiation, especially for haloperidol and levomepromazine with RR 9.9 (CI 95%, 9.6–10.2) and 19.1 (CI 95%, 18.5–19.8) respectively. The rest of the APS had a RR approximately 2. Long-term use (i.e. > 1 year) was also associated with increased risks for all agents but ziprasidone and chlorprothixen. The majority of agents demonstrated a dosedependent increase in RR and higher RR among individuals without dementia, compared with individuals with dementia. Conclusions.– Use of APS were associated with increased risks of mortality among elderly individuals, in particular during the first month after treatment initiation. Risk were comparable for most agents and was highest among people without diagnosed dementia. http://dx.doi.org/10.1016/j.eurger.2013.07.582 P515
Development of a European list of potentially inappropriate medication (PIM) for older adults: A consensus-based approach A. Renom Guiteras a , G. Meyer a , S. Bernard b , S. Holt-Noreiks b , P.A. Thürmann b,c a Witten/Herdecke University, Department of Nursing Science, Faculty of Health, Professorship of Clinical Nursing Science, Witten, Germany b Witten/Herdecke University, Department of Medicine, Faculty of Health, Chair of Clinical Pharmacology, Witten, Germany c Helios Clinic Wuppertal, Philipp Klee-Institut of Clinical Pharmacology, Wuppertal, Germany Introduction.– Several drugs are classified as potentially inappropriate for older adults because of their pharmacological effects and/or increased risk of adverse drug reactions. Different country-specific PIM-lists are available. A European PIM-list is lacking so far and is therefore in preparation in this project, nested in the 7th Framework European RightTimePlaceCare study. Methods.– (1) Development of a preliminary EU-PIM-list, based on the German PRISCUS-list, the French PIM-list (Laroche et al.), including drugs from other international PIM-lists (Beers, Fick et al., McLeod et al.). This list contains information on the main reasons why each drug may be PIM. (2) Recruitment of experts on geriatric prescription from Estonia, Finland, France, Netherlands, Spain and Sweden (n = 37). (3) Structured country-specific expansion of the preliminary list by (n = 8) experts. (4) Development of a final list using a two-round Delphi survey in which (n = 26) experts will assess the proposed drugs appropriateness, recommend dose adjustments and suggest therapeutic alternatives. (5) Validation of the list using recent prescription data from n = 2014 older adults with dementia from the same countries. Results.– Currently experts are participating in the second Delphiround. The final list will be available for validation in June 2013. Data on prescribing patterns and associations with health-related outcomes will be presented at the 9th Congress of the EUGMS in 2013. Key conclusions.– The European PIM-list will comprise specific drugs considered potentially inappropriate for older persons, as well as dose adjustments and therapeutic alternatives. The list can be used in clinical practice and for analysing and comparing prescribing patterns across several European countries. http://dx.doi.org/10.1016/j.eurger.2013.07.583 P516
Correlation of haloperidol levels in blood and cerebrospinal fluid: A pharmacokinetic study
9th congress of the EUGMS / European Geriatric Medicine 4 (2013) S142–S216
A.M. van Strien , A.M. Vermeulen Windsant-van den Tweel , P.M. Leliveld-van den Heuvel , M. di Biase , A.J. van den Brule , R.J. van Marum Jeroen Bosch Hospital, Den Bosch, The Netherlands Introduction.– Haloperidol is the first choice antipsychotic medication in treatment of delirium. In elderly there is a large, not well understood, inter-individual variation in effect and side effects (in particular antipsychotic induced Parkinsonism). There are three possible explanations. First, variation in transport over the bloodbrain barrier (BBB). Second, differences in pharmacogenetics. The genetically polymorphic enzyme Cytochroom P516 (CYP)-2D6 contributes to the biotransformation of haloperidol. Last, the number of dopamine-2 (D2) receptors in the brain. This is the first study that investigates, if variability can be explained by transport over the BBB. Methods.– This cross-sectional study included 20 elderly patients above 65 years (average 78.9 years), with an elevated risk of a delirium who were prescribed haloperidol 1 mg/day five days before an elective surgery with spinal anaesthesia. Introductory the surgery, cerebrospinal fluid (CSF) (2 mL) and a blood sample (2 mL) were taken. Sample analysis was done by a validated liquid chromatography–mass spectrometry. The correlation of plasma and CSF concentration of haloperidol was investigated by linear regression analysis. Results.– Serum and cerebrospinal fluid levels of haloperidol averaged 0.52 mcg/L (distribution 0.17–0.99 mcg/L) and 0.04 (distribution < 0.01–0.09 mcg/L) (ratio averaged 11.45%). The correlation of CSF and serum levels was significant (r = 0.853, P < 0.05). There is a large variation in serum levels (factor 6). Conclusions.– Variability in transport over the BBB is not the explanatory factor for inter-individual variation in response. Alternative explanations are variation in serum levels (due to cytochroom P516-2D6 polymorfisms) and variation in the number of remaining D2 receptors in the brain. http://dx.doi.org/10.1016/j.eurger.2013.07.584 P517
The FORTA Project 2013, “Fit for the aged”: Clinical approaches based on an innovative concept in geriatric pharmacology A.M. Kuhn-Thiel a,b , H. Frohnhofen a,b , M. Wehling a,b a Clin Pharmacol, Med Fac Mannheim, University of Heidelberg, Heidelberg, Germany b Knappschafts-Hospital, Teaching Hospital, University of Duisburg-Essen, Essen, Germany Introduction.– The pharmacotherapy of elderly multimorbid patients poses an increasing challenge in clinical practice. The FORTA concept is the first implicit listing approach in this context which involves both positive and negative labeling of commonly used medications for chronic illnesses (FORTA list) [1,2]. We aim to determine to what extent this system may help to rationalize pharmacotherapy of elderly patients. According to FORTA, medications belong to: Class A = (Absolutely): indispensible drug, clear-cut benefit; Class B = (Beneficial): proven efficacy but with safety concerns; Class C = (Careful): questionable efficacy/safety profiles, to be avoided or omitted when many other drugs are prescribed, review alternatives; or Class D = (Don’t): avoid in the elderly, omit first, review alternatives [3,4]. Methods.– This principle is currently being tested in a multicenter interventional study. The FORTA list is being developed as a clinical tool regarding implementation and utilization strategies. Results.– Results of a Delphi procedure conducted in 2012 involving 20 prominent experts in the field demonstrated high consensus val-
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ues for the evaluated drug labels and produced the revised FORTA list. Pilot studies conducted in Essen [5,6] tentatively indicate that implementation of FORTA may improve clinical outcomes (reduced fall risk, improved Barthel index). Key conclusions.– There is a considerable unmet medical need for clinical tools to aid physicians in drug prescribing and monitoring in their elderly patients. The FORTA concept requires continuous development in terms of listing, labeling and research into clinical utility. Further trials are needed to corroborate the promising clinical findings for the FORTA concept. References [1] Wehling M, Burkhardt H. Arzneitherapie für Ältere. 2nd ed Heidelberg: Springer; 2011 [in German]. [2] Wehling M. Drug therapy for the elderly. Vienna: Springer Publishers; 2013. [3] Wehling M. Drug therapy for the elderly: too much or too little, what to do? A new assessment system: fit for the aged FORTA. Dtsch Med Wochenschr 2008;133:2289–91. [4] Wehling M. Multimorbidity and polypharmacy: how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification: fit for the aged. J Am Geriatr Soc 2009;57:560–1. [5] Frohnhofen H, Michalek C, Wehling M. Assessment of drug treatment in geriatrics with the new FORTA criteria–Preliminary clinical experience. Dtsch Med Wochenschr 2011;136:1417–21 [in German]. [6] Frohnhofen H, Wehling M, Michalek C. Erste klinische Erfahrungen mit der neuen FORTA-Klassifikation (abstract). Z Gerontol Geriatr 2012;45:21 [in German]. http://dx.doi.org/10.1016/j.eurger.2013.07.585 P518
A randomized, double-blind, controlled trial of melatonin versus placebo in delirium A. de Jonghe , B.C. van Munster , J.C. Goslings , P. Kloen , C. van Rees , R. Wolvius , R. van Velde , M.M. Levi , R.J. de Haan , S.E. de Rooij , on behalf of the Amsterdam Delirium Study Academic Medical Centre, University of Amsterdam, Department of Internal Medicine, Geriatric section F4-218, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Background.– Older patients with cognitive impairment and dementia have a poor outcome after a hip fracture surgery, and about 30–50% of all those who sustain a hip fracture suffer from delirium. Circadian rhythm disturbances are characteristic for delirium. Melatonin influences the biological clock and might therefore be effective for reduction of the incidence and severity of delirium in older adults undergoing hip fracture repair. Methods.– In this multicentre double blind randomised controlled trial, we investigated the superiority of 3 mg melatonin versus placebo in preventing delirium in patients ≥ 65 years with hip fracture. Primary outcome was incidence of delirium, according to the DSM-IV criteria. Data were analysed according to the intention-totreat principle. Results.– Inclusion percentage was 62.3%, of the approached patients. Four hundred and fifty-two patients were randomised between November 2008 and May 2012. Mean age was 84 years, 63% lived at home before admission and 56% had cognitive impairment. There were no differences in the incidence of delirium, which occurred in 55 of the 186 patients (29.6%) receiving melatonin versus 49 of the 192 patients (25.5%) receiving placebo. In the melatonin group less patients experienced delirium a longer delirium episode (P = 0.02). There were no between-group differences in any of the other secondary outcomes, nor cognitive or functional outcomes at 3 months follow up.
9th congress of the EUGMS / European Geriatric Medicine 4 (2013) S142–S216
P513
Pressure ulcer treatment in the hospitalized patient – eHealth as a treatment strategy F. Vânia , M. Joana , S. Susana , M.P. Ana , P. Vítor C.H.U.C., Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal Introduction.– Costs associated with pressure ulcer treatment is high. Although strategies for prevention prove to be more costeffective, literature reviews demonstrate that approximately 5% of patients admitted develop pressure ulcers. Associated to this fact, is the number of people that already present pressure ulcers at the time of admission. Implementation of guidelines are very difficult. As such, if used correctly and as a decision-making support system, eHealth can improve knowledge and, consequently, improve patient care. Objective.– Improve treatment of pressure ulcers through an interactive digital board. Methods.–An interactive digital board was constructed using a decision-making algorithm based on NPUAP© guidelines and TIME algorithm. The algorithm was activated by filling the fields regarding PUSH-II assessment of the wound with two extra fields: odor and infection. After filling all the fields, the recommended treatment was shown. Data for time used for the wound care, materials used and total cost, were also assessed. Results.– In a total of 52 pressure ulcers, high rates of wound healing (56.7–100.0%) were observed though the monthly assessment, with an average cost of 2.51 D /category I, 5.39 D /category II, 6.14 D /category III and 6.21 D /category IV. PUSH-II scores showed overall improvement with the decrease of scores compared to the initial episode. Conclusions.– According to the results, the interactive digital board proves to be a good strategy for the implementation of changes in practice and introduction of guidelines. http://dx.doi.org/10.1016/j.eurger.2013.07.581 P514
Association of selected anti-psychotic agents with all-cause mortality in elderly individuals: A Danish Nationwide Cohort Study M. Sahlberg a , E. Holm b , T.S. Høj Jørgensen b , A. Højmann c , G.H. Gislason d , C. Torp-Pedersen e , C. Andersson d a Department of Geriatric Medicine, Aalborg University Hospital, Aalborg, Denmark b Department of Geriatric Medicine, Nykøbing-Falster Hospital, Nykøbing, Denmark c Department of Geriatric Medicine, Slagelse Hospital, Slagelse, Denmark d Department of Cardiology, Gentofte Hospital, Hellerup, Denmark e Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark Introduction.– In recent years data from observational studies have raised concerns about the safety of treatment with antipsychotic agents (APS) in elderly patients with dementia, but this area is still insufficiently investigated. We studied the outcomes associated with individual APS in elderly individuals using nationwide Danish data. Methods.– We included all individuals in Denmark aged 70 years or older between 1997 and 2009 who had not used APS prior to study baseline. Exposure to APS was assessed by identifying claimed prescriptions from pharmacies. Adjusted relative risks (RR) associated with exposure to APS were calculated by time-dependent Poisson regression models.
Results.– We included 1,235,869 individuals: 100,140 (8,1%) used APS at some point. For all agents, we found a highly increased RR of mortality during the first month after initiation, especially for haloperidol and levomepromazine with RR 9.9 (CI 95%, 9.6–10.2) and 19.1 (CI 95%, 18.5–19.8) respectively. The rest of the APS had a RR approximately 2. Long-term use (i.e. > 1 year) was also associated with increased risks for all agents but ziprasidone and chlorprothixen. The majority of agents demonstrated a dosedependent increase in RR and higher RR among individuals without dementia, compared with individuals with dementia. Conclusions.– Use of APS were associated with increased risks of mortality among elderly individuals, in particular during the first month after treatment initiation. Risk were comparable for most agents and was highest among people without diagnosed dementia. http://dx.doi.org/10.1016/j.eurger.2013.07.582 P515
Development of a European list of potentially inappropriate medication (PIM) for older adults: A consensus-based approach A. Renom Guiteras a , G. Meyer a , S. Bernard b , S. Holt-Noreiks b , P.A. Thürmann b,c a Witten/Herdecke University, Department of Nursing Science, Faculty of Health, Professorship of Clinical Nursing Science, Witten, Germany b Witten/Herdecke University, Department of Medicine, Faculty of Health, Chair of Clinical Pharmacology, Witten, Germany c Helios Clinic Wuppertal, Philipp Klee-Institut of Clinical Pharmacology, Wuppertal, Germany Introduction.– Several drugs are classified as potentially inappropriate for older adults because of their pharmacological effects and/or increased risk of adverse drug reactions. Different country-specific PIM-lists are available. A European PIM-list is lacking so far and is therefore in preparation in this project, nested in the 7th Framework European RightTimePlaceCare study. Methods.– (1) Development of a preliminary EU-PIM-list, based on the German PRISCUS-list, the French PIM-list (Laroche et al.), including drugs from other international PIM-lists (Beers, Fick et al., McLeod et al.). This list contains information on the main reasons why each drug may be PIM. (2) Recruitment of experts on geriatric prescription from Estonia, Finland, France, Netherlands, Spain and Sweden (n = 37). (3) Structured country-specific expansion of the preliminary list by (n = 8) experts. (4) Development of a final list using a two-round Delphi survey in which (n = 26) experts will assess the proposed drugs appropriateness, recommend dose adjustments and suggest therapeutic alternatives. (5) Validation of the list using recent prescription data from n = 2014 older adults with dementia from the same countries. Results.– Currently experts are participating in the second Delphiround. The final list will be available for validation in June 2013. Data on prescribing patterns and associations with health-related outcomes will be presented at the 9th Congress of the EUGMS in 2013. Key conclusions.– The European PIM-list will comprise specific drugs considered potentially inappropriate for older persons, as well as dose adjustments and therapeutic alternatives. The list can be used in clinical practice and for analysing and comparing prescribing patterns across several European countries. http://dx.doi.org/10.1016/j.eurger.2013.07.583 P516
Correlation of haloperidol levels in blood and cerebrospinal fluid: A pharmacokinetic study
9th congress of the EUGMS / European Geriatric Medicine 4 (2013) S142–S216
A.M. van Strien , A.M. Vermeulen Windsant-van den Tweel , P.M. Leliveld-van den Heuvel , M. di Biase , A.J. van den Brule , R.J. van Marum Jeroen Bosch Hospital, Den Bosch, The Netherlands Introduction.– Haloperidol is the first choice antipsychotic medication in treatment of delirium. In elderly there is a large, not well understood, inter-individual variation in effect and side effects (in particular antipsychotic induced Parkinsonism). There are three possible explanations. First, variation in transport over the bloodbrain barrier (BBB). Second, differences in pharmacogenetics. The genetically polymorphic enzyme Cytochroom P516 (CYP)-2D6 contributes to the biotransformation of haloperidol. Last, the number of dopamine-2 (D2) receptors in the brain. This is the first study that investigates, if variability can be explained by transport over the BBB. Methods.– This cross-sectional study included 20 elderly patients above 65 years (average 78.9 years), with an elevated risk of a delirium who were prescribed haloperidol 1 mg/day five days before an elective surgery with spinal anaesthesia. Introductory the surgery, cerebrospinal fluid (CSF) (2 mL) and a blood sample (2 mL) were taken. Sample analysis was done by a validated liquid chromatography–mass spectrometry. The correlation of plasma and CSF concentration of haloperidol was investigated by linear regression analysis. Results.– Serum and cerebrospinal fluid levels of haloperidol averaged 0.52 mcg/L (distribution 0.17–0.99 mcg/L) and 0.04 (distribution < 0.01–0.09 mcg/L) (ratio averaged 11.45%). The correlation of CSF and serum levels was significant (r = 0.853, P < 0.05). There is a large variation in serum levels (factor 6). Conclusions.– Variability in transport over the BBB is not the explanatory factor for inter-individual variation in response. Alternative explanations are variation in serum levels (due to cytochroom P516-2D6 polymorfisms) and variation in the number of remaining D2 receptors in the brain. http://dx.doi.org/10.1016/j.eurger.2013.07.584 P517
The FORTA Project 2013, “Fit for the aged”: Clinical approaches based on an innovative concept in geriatric pharmacology A.M. Kuhn-Thiel a,b , H. Frohnhofen a,b , M. Wehling a,b a Clin Pharmacol, Med Fac Mannheim, University of Heidelberg, Heidelberg, Germany b Knappschafts-Hospital, Teaching Hospital, University of Duisburg-Essen, Essen, Germany Introduction.– The pharmacotherapy of elderly multimorbid patients poses an increasing challenge in clinical practice. The FORTA concept is the first implicit listing approach in this context which involves both positive and negative labeling of commonly used medications for chronic illnesses (FORTA list) [1,2]. We aim to determine to what extent this system may help to rationalize pharmacotherapy of elderly patients. According to FORTA, medications belong to: Class A = (Absolutely): indispensible drug, clear-cut benefit; Class B = (Beneficial): proven efficacy but with safety concerns; Class C = (Careful): questionable efficacy/safety profiles, to be avoided or omitted when many other drugs are prescribed, review alternatives; or Class D = (Don’t): avoid in the elderly, omit first, review alternatives [3,4]. Methods.– This principle is currently being tested in a multicenter interventional study. The FORTA list is being developed as a clinical tool regarding implementation and utilization strategies. Results.– Results of a Delphi procedure conducted in 2012 involving 20 prominent experts in the field demonstrated high consensus val-
S175
ues for the evaluated drug labels and produced the revised FORTA list. Pilot studies conducted in Essen [5,6] tentatively indicate that implementation of FORTA may improve clinical outcomes (reduced fall risk, improved Barthel index). Key conclusions.– There is a considerable unmet medical need for clinical tools to aid physicians in drug prescribing and monitoring in their elderly patients. The FORTA concept requires continuous development in terms of listing, labeling and research into clinical utility. Further trials are needed to corroborate the promising clinical findings for the FORTA concept. References [1] Wehling M, Burkhardt H. Arzneitherapie für Ältere. 2nd ed Heidelberg: Springer; 2011 [in German]. [2] Wehling M. Drug therapy for the elderly. Vienna: Springer Publishers; 2013. [3] Wehling M. Drug therapy for the elderly: too much or too little, what to do? A new assessment system: fit for the aged FORTA. Dtsch Med Wochenschr 2008;133:2289–91. [4] Wehling M. Multimorbidity and polypharmacy: how to reduce the harmful drug load and yet add needed drugs in the elderly? Proposal of a new drug classification: fit for the aged. J Am Geriatr Soc 2009;57:560–1. [5] Frohnhofen H, Michalek C, Wehling M. Assessment of drug treatment in geriatrics with the new FORTA criteria–Preliminary clinical experience. Dtsch Med Wochenschr 2011;136:1417–21 [in German]. [6] Frohnhofen H, Wehling M, Michalek C. Erste klinische Erfahrungen mit der neuen FORTA-Klassifikation (abstract). Z Gerontol Geriatr 2012;45:21 [in German]. http://dx.doi.org/10.1016/j.eurger.2013.07.585 P518
A randomized, double-blind, controlled trial of melatonin versus placebo in delirium A. de Jonghe , B.C. van Munster , J.C. Goslings , P. Kloen , C. van Rees , R. Wolvius , R. van Velde , M.M. Levi , R.J. de Haan , S.E. de Rooij , on behalf of the Amsterdam Delirium Study Academic Medical Centre, University of Amsterdam, Department of Internal Medicine, Geriatric section F4-218, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands Background.– Older patients with cognitive impairment and dementia have a poor outcome after a hip fracture surgery, and about 30–50% of all those who sustain a hip fracture suffer from delirium. Circadian rhythm disturbances are characteristic for delirium. Melatonin influences the biological clock and might therefore be effective for reduction of the incidence and severity of delirium in older adults undergoing hip fracture repair. Methods.– In this multicentre double blind randomised controlled trial, we investigated the superiority of 3 mg melatonin versus placebo in preventing delirium in patients ≥ 65 years with hip fracture. Primary outcome was incidence of delirium, according to the DSM-IV criteria. Data were analysed according to the intention-totreat principle. Results.– Inclusion percentage was 62.3%, of the approached patients. Four hundred and fifty-two patients were randomised between November 2008 and May 2012. Mean age was 84 years, 63% lived at home before admission and 56% had cognitive impairment. There were no differences in the incidence of delirium, which occurred in 55 of the 186 patients (29.6%) receiving melatonin versus 49 of the 192 patients (25.5%) receiving placebo. In the melatonin group less patients experienced delirium a longer delirium episode (P = 0.02). There were no between-group differences in any of the other secondary outcomes, nor cognitive or functional outcomes at 3 months follow up.