- Email: [email protected]
Propofol Infusion for the Retrieval of the Acutely Psychotic Patient
CASE STUDY
Propofol Infusion for the Retrieval of the Acutely Psychotic Patient Richard Chalwin, MBChB, FCICM
Abstract Transporting acutely psychotic patients is hazardous because of the risks they present to themselves, escorting staff, and aircraft. Various strategies have been proposed, usually involving combinations of sedating drugs and physical restraint. Thus far, none guarantees safe retrieval while completely mitigating risks. This case proposes the use of propofol as an alternative to more traditionally used agents. An infusion facilitated the uneventful and safe retrieval of a patient who had demonstrated resistance and tolerance to other drugs. Discussion is also presented on the potential utility of propofol for the retrieval of acutely psychotic patients.
Introduction The acutely psychotic patient presents many management challenges. Those are amplified when these patients must be transported between hospitals. Facilitating retrieval in a safe manner requires addressing potential risks to the patient, staff, and transport platform. No consensus has been achieved regarding how to achieve this, but most guidelines involve combinations of pharmacological agents.1-5 Although these can create a passive patient, they have many undesirable side effects. This case report proposes the use of propofol for short-acting, dose-dependent sedation.
Case Report This case concerns a 45-year-old man with schizoaffective disorder normally managed as an outpatient in a rural town. One morning in March 2009, he developed an acute psychotic episode with no obvious precipitant and became violent and abusive. His family requested police intervention; however, after 8 hours of detention in their cells, it became obvious that inpatient admission was required. He was brought to the town hospital, still manifestly psychotic, exhibiting both verbal and physical aggression. With
Lyell McEwin Hospital, Elzabeth Vale, Australia Address for correspondence Richard Chalwin, Lyell McEwin Hospital, Intensive Care Unit, Haydown Road, Elzabeth Vale, SA 5112, Australia, [email protected] 1067-991X/$36.00 Copyright 2012 Air Medical Journal Associates doi:10.1016/j.amj.2011.06.008 January-February 2012
the assistance of the police, who provided physical restraint, the medical team secured intravenous access and administered a combination of olanzapine and benzodiazepines, with some initial success in reducing his state of delirium. Unfortunately, overnight he became tolerant to these agents, and his level of agitation steadily increased. Retrieval to a secure psychiatric facility was requested because he was overwhelming the very limited local psychiatric services provided by a lone mental health nurse. Our emergency medical retrieval service was tasked with transporting him to the state tertiary psychiatric hospital, and the author and a flight nurse attended the patient. We arrived approximately 18 hours after his admission to the referring center. The patient had been physically restrained with hard shackles yet was still requiring additional restraint by nurses and hospital security officers because of his continuing aggressive behavior. He was still expressing profoundly paranoid delusions, mostly centered on negative perceptions of his medical and psychiatric treatment, and a complete lack of insight. Physical examination and measurement of observations were impossible because of his noncompliance; however, no overt hemodynamic or respiratory compromise was evident. During the past 18 hours of his admission, he had received 40 mg olanzapine oral wafers, 30 mg intravenous midazolam, and 5 mg intravenous clonazepam, but these agents appeared to have achieved little control of his degree of psychosis. Rather than persist with increasing doses of similar agents with the potential to magnify the risk of adverse side effects, we tried a small bolus dose (20 mg) of Propofol (Fresofol 1% wt/vol Injection, Fresenius Kabi, Pymble, New South Wales). This achieved rapid conscious sedation, leading to satisfactory patient compliance with healthcare interventions. His psychosis seemed to be almost completely suppressed, as he was able to appropriately answer questions in a yes/no fashion. The flight nurse and the author then commenced an infusion of propofol titrated to maintain a state of light sedation with ready rousability. This was achieved with an infusion rate range of 3 to 5mL/hour (e.g., 0.3 to 0.5 mg/kg/hour, based on an estimated body weight of 100 kg) and three additional 20 mg boluses during the retrieval. Physical restraints were applied for the return flight but not actually required because of the effectiveness of the propofol infusion in maintaining compliance. 33
The patient was fully monitored and observed by our team at all stages of the retrieval. He experienced none of the recognized side effects of propofol while receiving the infusion. In particular, we recorded no episodes of hypotension (nadir systolic blood pressure 100 mmHg), respiratory depression (nadir respiratory rate 18 breaths/min) or desaturation (nadir pulse oximetry 96% with 2 L/min of supplementary oxygen delivered by nasal cannulae and a maximum cabin altitude of 6,000 feet above sea level). The patient was safely delivered to the receiving center with no apparent adverse sequelae from the propofol. Of interest, we observed a relapse in his level of agitation after cessation of the propofol infusion while packing up before returning to our operating base.
Discussion Aeromedical transport of psychiatric patients is becoming increasingly common. Yet such patients present unique challenges and hazards to the escorting staff and the aerial platform.6 The recommendations in most guidelines have to be encompassing rather than specific because of the unpredictable nature of psychiatric patients.1-5 A significant issue facing the retrieval team is choice of chemical restraint. Many patients are tolerant of the effects of antipsychotic agents and benzodiazepines. Yet combinations of those classes of drugs still form the core of most pharmacological regimens.1-4, 7-11 With increasing dose comes the risk of side effects. Thus, a search for alternative agents would be worthwhile, the aim being to find a drug, or combination of drugs, that facilitates a reduction in symptoms for the patient and amelioration of risks to attending staff. A concurrent priority is to avoid intubation at all costs, because this confers additional considerable morbidity.4,12 The British Columbia Ambulance Service Air Ambulance Program has modified the standard protocol, as covered above, with the addition of a sedating antihistamine antiemetic agent.5 This is an ingenious concept using a drug’s side effect to our benefit. However, the sedative effect of antihistamines is unpredictable and cannot be titrated. Other suggestions include the use of high-dose midazolam and thiopentone.13,14 Although apparently achieving good results, these regimens carry considerable risks. Both were reported in the emergency department setting, where the availability of additional staff, limitless space, and advanced resuscitation equipment justify the potential for adverse events. The space- and resource-poor environment of retrieval aircraft shifts the balance away from benefit. An additional concern is that both are relatively long-acting agents and, therefore, less easy to titrate, which can result in unnecessarily extended periods of sedation. Ketamine is another promising therapy in the prehospital setting. Its use has been described both in the military and civilian services with apparent success.15-17 Ketamine has many beneficial attributes, the most important being its stimulation of respiratory drive, in stark contrast with the depressant effect of most 34
other sedative agents. However, it has a number of undesirable side effects remain, and the drug is yet to be fully validated. To the knowledge of the author, no reports exist describing the use of propofol for sedation of psychiatric patients in the prehospital environment. Fox and Bostwick described the successful use of propofol in an acutely agitated patient who was failing to respond to other therapies.18 However, they managed him in an intensive care unit for the duration of the propofol infusion. A more recent report by Cluver and Hardesty similarly reported resolution of acute psychosis with propofol.19 Again, patient management occurred in the intensive care unit on grounds of safety concerns. Interestingly, in both cases artificial ventilation was not required, and drug tolerance seemed good. Propofol is now commonplace for procedural sedation.20 Gastroenterologists, amongst others, have devised intricate administration policies for achieving conscious sedation; that is a drowsy yet cooperative patient. The wealth of collected data seem to validate the safety profile of low-dose propofol infusions outside of the critical care setting.21 Although less recognized, propofol also has a role in the emergency department for sedation during cardioversion or orthopedic manipulation. A recent systematic review found equivalent rates of success, as well as adverse events, when directly compared with midazolam, an accepted emergency sedating agent with its own issues.22 As with any drug, propofol has many advantages and disadvantages.23 It is often disregarded as mainly an anesthetic agent because of the risks of respiratory depression, cardiovascular compromise, and depressant effects on airway reflexes. As such, propofol should not be used casually. However, it has a favorable dose-dependence, which allows for considerable leeway in titration. Central nervous system effects range from anxiolysis and mood stabilization through increasing levels of sedation to coma. This means it could be used in the agitated psychiatric patient to titrate the desired level of sedation, with the backup facility of also acting as an induction agent if intubation is required. Propofol has more favorable attributes that suit it to a role in the retrieval of psychiatric patients. First, while acting principally as a gamma-amino-butyric-acid agonist, it is also thought to work at other neurotransmitter receptors, which may assist with the sedation of patients who have shown tolerance to the limited actions of benzodiazepines or dopamine antagonists. Second, it seems to have a purely depressant effect, with no reported cases of paradoxical agitation as seen with midazolam and other benzodiazepines.24 Third, propofol is quick both in onset to and offset from action. Therefore, any inadvertent overdosage will rapidly self-correct. Finally, of great usefulness in the air medical environment, it also acts as an antiemetic. This is especially important because psychiatric patients are usually physically restrained for flight; therefore, repositioning in the event of vomiting is hindered. So, to summarize, propofol seems to offer many benefits because of its favorable pharmacokinetic and pharmacodyAir Medical Journal 31:1
namic characteristics. It does present its own unique risks, but these can usually be mitigated by careful titration of dosing and limiting use to experienced clinicians. Prospective clinical trials would help investigate whether it can be safely added to the retrieval team armamentarium for difficult psychiatric patients.
References 1. Broadstock M. The effectiveness and safety of drug treatment for urgent sedation in psychiatric emergencies. A critical appraisal of the literature. NZHTA Report 2001; 4(1). 2. National Association of EMS Physicians Position Paper. Patient restraint in emergency medical services systems. PreHosp Emerg Care 2002;6:340-5. 3. Department of Human Services Mental Health Services and Programs. A new millennium, a new beginning: mental health in South Australia emergency transport of mental health consumers from country locations: policy and procedure series 20022005. EDM P7-02. December 2002. 4. National Mental Health Working Group. National safety priorities in mental health: a national plan for reducing harm, Health Priorities and Suicide Prevention Branch, Department of Health and Ageing, Commonwealth of Australia, Canberra. October 2005. 5. Wheeler S, Wong B, MD, L’Heureux R. Criteria for sedation of psychiatric patients for air transport in British Columbia. British Columbia Med J 2009;51:346-9. 6. Pierson K, Power Y, Marcus A, Dahlberg A. Airline passenger misconduct: management implications for physicians. Aviat Space Environ Med 2007;78:361–7. 7. Hughes D. Acute psychopharmacological management of the aggressive psychotic patient. Psychiatric Services 1999;50:1135-7. 8. Western Australian Therapeutics Advisory Group. Sedation of acutely agitated adult patients prior to transportation: a guide for medical practitioners. Version 1. January 2006. 9. Byrne P. Managing the acute psychotic episode. BMJ 2007;334:686-92. 10. Keks N, Blashki G. The acutely psychotic patient: Assessment and initial management. Aust Fam Physician 2006;35:90-4. 11. Bruce M, Thayer K. Prehospital management of the psychotic and aggressive patient with bipolar disease. Available at http://www.emsresponder.com/online/printer .jsp?id⫽2637. Accessed April 2011. 12. Muakkassa FF, Marley RA, Workman MC, Salvator AE. Hospital outcomes and disposition of trauma patients who are intubated because of combativeness. J Trauma 2010;68:1305-9. 13. Spain D, Crilly J, Whyte I, Jenner L, Carr V, Baker A. Safety and effectiveness of high-dose midazolam for severe behavioural disturbance in an emergency department with suspected psychostimulant-affected patients. Emerg Med Aust 2008;20:112-20. 14. Howes MC, van Rensburg WJ. Thiopentone sedation for sedation of acutely agitated, violent, intoxicated patients: Evaluation of 2 cases. Int J Emerg Med 2009;2:47-49. 15. Melamed E, Oron Y, Ben-Avraham R, Blumenfeld A, Lin G. The combative multitrauma patient: a protocol for prehospital management. Euro J Emerg Med 2007;14:265. 16. Svenson JE, Abernathy MK. Ketamine for prehospital use: new look at an old drug. Am J Emerg Med 2007;25:977-80. 17. Roberts JR, Geeting GK. Intramuscular ketamine for the rapid tranquilization of the uncontrollable, violent, and dangerous adult patient. J Trauma 2001;51:1008-10. 18. Fox FL, Bostwick JM. Propofol sedation of refractory delirious mania. Psychosomatics 1997;38:288-90. 19. Cluver JS, Hardesty SJ. Propofol for severe, refractory mania: a case report. J Clin Psychiatry 2006;67:165-6. 20. Vargo JJ. Procedural sedation. Curr Opin Gastroenterol 2010;26:421-4. 21. Rex DK, Deenadayalu VP, Eid E, et al. Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology 2009;137:1229-37. 22. Hohl CM, Sadatsafavi M, Nosyk B, Anis AH. Safety and clinical effectiveness of midazolam versus propofol for procedural sedation in the emergency department: a systematic review. Acad Emerg Med 2008;15:1-8. 23. Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharmaceutical Design 2004;10:3639-49. 24. Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy 2004;24:1177-85.
January-February 2012
35
Propofol Infusion for the Retrieval of the Acutely Psychotic Patient Richard Chalwin, MBChB, FCICM
Abstract Transporting acutely psychotic patients is hazardous because of the risks they present to themselves, escorting staff, and aircraft. Various strategies have been proposed, usually involving combinations of sedating drugs and physical restraint. Thus far, none guarantees safe retrieval while completely mitigating risks. This case proposes the use of propofol as an alternative to more traditionally used agents. An infusion facilitated the uneventful and safe retrieval of a patient who had demonstrated resistance and tolerance to other drugs. Discussion is also presented on the potential utility of propofol for the retrieval of acutely psychotic patients.
Introduction The acutely psychotic patient presents many management challenges. Those are amplified when these patients must be transported between hospitals. Facilitating retrieval in a safe manner requires addressing potential risks to the patient, staff, and transport platform. No consensus has been achieved regarding how to achieve this, but most guidelines involve combinations of pharmacological agents.1-5 Although these can create a passive patient, they have many undesirable side effects. This case report proposes the use of propofol for short-acting, dose-dependent sedation.
Case Report This case concerns a 45-year-old man with schizoaffective disorder normally managed as an outpatient in a rural town. One morning in March 2009, he developed an acute psychotic episode with no obvious precipitant and became violent and abusive. His family requested police intervention; however, after 8 hours of detention in their cells, it became obvious that inpatient admission was required. He was brought to the town hospital, still manifestly psychotic, exhibiting both verbal and physical aggression. With
Lyell McEwin Hospital, Elzabeth Vale, Australia Address for correspondence Richard Chalwin, Lyell McEwin Hospital, Intensive Care Unit, Haydown Road, Elzabeth Vale, SA 5112, Australia, [email protected] 1067-991X/$36.00 Copyright 2012 Air Medical Journal Associates doi:10.1016/j.amj.2011.06.008 January-February 2012
the assistance of the police, who provided physical restraint, the medical team secured intravenous access and administered a combination of olanzapine and benzodiazepines, with some initial success in reducing his state of delirium. Unfortunately, overnight he became tolerant to these agents, and his level of agitation steadily increased. Retrieval to a secure psychiatric facility was requested because he was overwhelming the very limited local psychiatric services provided by a lone mental health nurse. Our emergency medical retrieval service was tasked with transporting him to the state tertiary psychiatric hospital, and the author and a flight nurse attended the patient. We arrived approximately 18 hours after his admission to the referring center. The patient had been physically restrained with hard shackles yet was still requiring additional restraint by nurses and hospital security officers because of his continuing aggressive behavior. He was still expressing profoundly paranoid delusions, mostly centered on negative perceptions of his medical and psychiatric treatment, and a complete lack of insight. Physical examination and measurement of observations were impossible because of his noncompliance; however, no overt hemodynamic or respiratory compromise was evident. During the past 18 hours of his admission, he had received 40 mg olanzapine oral wafers, 30 mg intravenous midazolam, and 5 mg intravenous clonazepam, but these agents appeared to have achieved little control of his degree of psychosis. Rather than persist with increasing doses of similar agents with the potential to magnify the risk of adverse side effects, we tried a small bolus dose (20 mg) of Propofol (Fresofol 1% wt/vol Injection, Fresenius Kabi, Pymble, New South Wales). This achieved rapid conscious sedation, leading to satisfactory patient compliance with healthcare interventions. His psychosis seemed to be almost completely suppressed, as he was able to appropriately answer questions in a yes/no fashion. The flight nurse and the author then commenced an infusion of propofol titrated to maintain a state of light sedation with ready rousability. This was achieved with an infusion rate range of 3 to 5mL/hour (e.g., 0.3 to 0.5 mg/kg/hour, based on an estimated body weight of 100 kg) and three additional 20 mg boluses during the retrieval. Physical restraints were applied for the return flight but not actually required because of the effectiveness of the propofol infusion in maintaining compliance. 33
The patient was fully monitored and observed by our team at all stages of the retrieval. He experienced none of the recognized side effects of propofol while receiving the infusion. In particular, we recorded no episodes of hypotension (nadir systolic blood pressure 100 mmHg), respiratory depression (nadir respiratory rate 18 breaths/min) or desaturation (nadir pulse oximetry 96% with 2 L/min of supplementary oxygen delivered by nasal cannulae and a maximum cabin altitude of 6,000 feet above sea level). The patient was safely delivered to the receiving center with no apparent adverse sequelae from the propofol. Of interest, we observed a relapse in his level of agitation after cessation of the propofol infusion while packing up before returning to our operating base.
Discussion Aeromedical transport of psychiatric patients is becoming increasingly common. Yet such patients present unique challenges and hazards to the escorting staff and the aerial platform.6 The recommendations in most guidelines have to be encompassing rather than specific because of the unpredictable nature of psychiatric patients.1-5 A significant issue facing the retrieval team is choice of chemical restraint. Many patients are tolerant of the effects of antipsychotic agents and benzodiazepines. Yet combinations of those classes of drugs still form the core of most pharmacological regimens.1-4, 7-11 With increasing dose comes the risk of side effects. Thus, a search for alternative agents would be worthwhile, the aim being to find a drug, or combination of drugs, that facilitates a reduction in symptoms for the patient and amelioration of risks to attending staff. A concurrent priority is to avoid intubation at all costs, because this confers additional considerable morbidity.4,12 The British Columbia Ambulance Service Air Ambulance Program has modified the standard protocol, as covered above, with the addition of a sedating antihistamine antiemetic agent.5 This is an ingenious concept using a drug’s side effect to our benefit. However, the sedative effect of antihistamines is unpredictable and cannot be titrated. Other suggestions include the use of high-dose midazolam and thiopentone.13,14 Although apparently achieving good results, these regimens carry considerable risks. Both were reported in the emergency department setting, where the availability of additional staff, limitless space, and advanced resuscitation equipment justify the potential for adverse events. The space- and resource-poor environment of retrieval aircraft shifts the balance away from benefit. An additional concern is that both are relatively long-acting agents and, therefore, less easy to titrate, which can result in unnecessarily extended periods of sedation. Ketamine is another promising therapy in the prehospital setting. Its use has been described both in the military and civilian services with apparent success.15-17 Ketamine has many beneficial attributes, the most important being its stimulation of respiratory drive, in stark contrast with the depressant effect of most 34
other sedative agents. However, it has a number of undesirable side effects remain, and the drug is yet to be fully validated. To the knowledge of the author, no reports exist describing the use of propofol for sedation of psychiatric patients in the prehospital environment. Fox and Bostwick described the successful use of propofol in an acutely agitated patient who was failing to respond to other therapies.18 However, they managed him in an intensive care unit for the duration of the propofol infusion. A more recent report by Cluver and Hardesty similarly reported resolution of acute psychosis with propofol.19 Again, patient management occurred in the intensive care unit on grounds of safety concerns. Interestingly, in both cases artificial ventilation was not required, and drug tolerance seemed good. Propofol is now commonplace for procedural sedation.20 Gastroenterologists, amongst others, have devised intricate administration policies for achieving conscious sedation; that is a drowsy yet cooperative patient. The wealth of collected data seem to validate the safety profile of low-dose propofol infusions outside of the critical care setting.21 Although less recognized, propofol also has a role in the emergency department for sedation during cardioversion or orthopedic manipulation. A recent systematic review found equivalent rates of success, as well as adverse events, when directly compared with midazolam, an accepted emergency sedating agent with its own issues.22 As with any drug, propofol has many advantages and disadvantages.23 It is often disregarded as mainly an anesthetic agent because of the risks of respiratory depression, cardiovascular compromise, and depressant effects on airway reflexes. As such, propofol should not be used casually. However, it has a favorable dose-dependence, which allows for considerable leeway in titration. Central nervous system effects range from anxiolysis and mood stabilization through increasing levels of sedation to coma. This means it could be used in the agitated psychiatric patient to titrate the desired level of sedation, with the backup facility of also acting as an induction agent if intubation is required. Propofol has more favorable attributes that suit it to a role in the retrieval of psychiatric patients. First, while acting principally as a gamma-amino-butyric-acid agonist, it is also thought to work at other neurotransmitter receptors, which may assist with the sedation of patients who have shown tolerance to the limited actions of benzodiazepines or dopamine antagonists. Second, it seems to have a purely depressant effect, with no reported cases of paradoxical agitation as seen with midazolam and other benzodiazepines.24 Third, propofol is quick both in onset to and offset from action. Therefore, any inadvertent overdosage will rapidly self-correct. Finally, of great usefulness in the air medical environment, it also acts as an antiemetic. This is especially important because psychiatric patients are usually physically restrained for flight; therefore, repositioning in the event of vomiting is hindered. So, to summarize, propofol seems to offer many benefits because of its favorable pharmacokinetic and pharmacodyAir Medical Journal 31:1
namic characteristics. It does present its own unique risks, but these can usually be mitigated by careful titration of dosing and limiting use to experienced clinicians. Prospective clinical trials would help investigate whether it can be safely added to the retrieval team armamentarium for difficult psychiatric patients.
References 1. Broadstock M. The effectiveness and safety of drug treatment for urgent sedation in psychiatric emergencies. A critical appraisal of the literature. NZHTA Report 2001; 4(1). 2. National Association of EMS Physicians Position Paper. Patient restraint in emergency medical services systems. PreHosp Emerg Care 2002;6:340-5. 3. Department of Human Services Mental Health Services and Programs. A new millennium, a new beginning: mental health in South Australia emergency transport of mental health consumers from country locations: policy and procedure series 20022005. EDM P7-02. December 2002. 4. National Mental Health Working Group. National safety priorities in mental health: a national plan for reducing harm, Health Priorities and Suicide Prevention Branch, Department of Health and Ageing, Commonwealth of Australia, Canberra. October 2005. 5. Wheeler S, Wong B, MD, L’Heureux R. Criteria for sedation of psychiatric patients for air transport in British Columbia. British Columbia Med J 2009;51:346-9. 6. Pierson K, Power Y, Marcus A, Dahlberg A. Airline passenger misconduct: management implications for physicians. Aviat Space Environ Med 2007;78:361–7. 7. Hughes D. Acute psychopharmacological management of the aggressive psychotic patient. Psychiatric Services 1999;50:1135-7. 8. Western Australian Therapeutics Advisory Group. Sedation of acutely agitated adult patients prior to transportation: a guide for medical practitioners. Version 1. January 2006. 9. Byrne P. Managing the acute psychotic episode. BMJ 2007;334:686-92. 10. Keks N, Blashki G. The acutely psychotic patient: Assessment and initial management. Aust Fam Physician 2006;35:90-4. 11. Bruce M, Thayer K. Prehospital management of the psychotic and aggressive patient with bipolar disease. Available at http://www.emsresponder.com/online/printer .jsp?id⫽2637. Accessed April 2011. 12. Muakkassa FF, Marley RA, Workman MC, Salvator AE. Hospital outcomes and disposition of trauma patients who are intubated because of combativeness. J Trauma 2010;68:1305-9. 13. Spain D, Crilly J, Whyte I, Jenner L, Carr V, Baker A. Safety and effectiveness of high-dose midazolam for severe behavioural disturbance in an emergency department with suspected psychostimulant-affected patients. Emerg Med Aust 2008;20:112-20. 14. Howes MC, van Rensburg WJ. Thiopentone sedation for sedation of acutely agitated, violent, intoxicated patients: Evaluation of 2 cases. Int J Emerg Med 2009;2:47-49. 15. Melamed E, Oron Y, Ben-Avraham R, Blumenfeld A, Lin G. The combative multitrauma patient: a protocol for prehospital management. Euro J Emerg Med 2007;14:265. 16. Svenson JE, Abernathy MK. Ketamine for prehospital use: new look at an old drug. Am J Emerg Med 2007;25:977-80. 17. Roberts JR, Geeting GK. Intramuscular ketamine for the rapid tranquilization of the uncontrollable, violent, and dangerous adult patient. J Trauma 2001;51:1008-10. 18. Fox FL, Bostwick JM. Propofol sedation of refractory delirious mania. Psychosomatics 1997;38:288-90. 19. Cluver JS, Hardesty SJ. Propofol for severe, refractory mania: a case report. J Clin Psychiatry 2006;67:165-6. 20. Vargo JJ. Procedural sedation. Curr Opin Gastroenterol 2010;26:421-4. 21. Rex DK, Deenadayalu VP, Eid E, et al. Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology 2009;137:1229-37. 22. Hohl CM, Sadatsafavi M, Nosyk B, Anis AH. Safety and clinical effectiveness of midazolam versus propofol for procedural sedation in the emergency department: a systematic review. Acad Emerg Med 2008;15:1-8. 23. Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharmaceutical Design 2004;10:3639-49. 24. Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy 2004;24:1177-85.
January-February 2012
35