This thesis consists of two studies presented as two separate manuscripts (one has been published in a peer-reviewed journal and the other is in the process of being submitted to a peer-reviewed journal) and a protocol for a pilot randomized controlled trial. The overarching aim of this thesis was to explore the evidence examining the use of ketamine as a sedative for critically ill mechanically ventilated patients in the Intensive Care Unit (ICU). We conducted a national survey to understand the beliefs and practices of Canadian ICU physicians regarding the use of ketamine as a continuous intravenous sedative in critically ill patients and to gauge interest in participating in a randomized controlled trial (RCT). We surveyed 400 physician members of the Canadian Critical Care Society and found that most respondents rarely use ketamine as a continuous infusion for sedation or analgesia in the ICU. We found that there were a number of clinical circumstances that would make physicians more likely to use ketamine such as asthma exacerbation and established tolerance to opioids. Conversely, physicians were concerned about the potential side effects of ketamine, particularly psychotropic effects including delirium. Overall, the majority of physicians surveyed agreed that there is a need for a clinical trial to evaluate the effectiveness and safety of ketamine as a sedative infusion in the ICU. The results of this survey informed the second manuscript which is a systematic review examining the use of procedural sedation medications in acutely ill patients. Prospective data examining ketamine as a continuous sedative in critically ill patients is sparse and insufficient for pooled analysis. Therefore, we focused on an indirect source of evidence, the role of ketamine as a procedural sedation drug. In order to summarize this data, we performed a systematic review and network meta-analysis (NMA) comparing all peri-procedural sedative drugs in acutely ill patients. The NMA provides the ability to include indirect data into the pooled point estimates. We performed a search of multiple databases and found 82 RCTs (8,105 patients) that met eligibility criteria, 78 conducted in the Emergency Department and 4 in the ICU. Compared to alternative medications, we found that ketamine was associated with the fewest respiratory adverse events based on high certainty evidence. Furthermore, we found that combining ketamine with propofol resulted in the highest patient satisfaction (high certainty) and the fewest cardiac adverse events (low certainty). The final component of this thesis is a pilot RCT protocol examining the feasibility of a larger RCT assessing the efficacy and safety of an adjunctive ketamine continuous infusion in mechanically ventilated ICU patients. We plan to submit this protocol for peer-reviewed funding as a first step to address this clinically important question. / Thesis / Master of Health Sciences (MSc)

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This study was designed to evaluate the efficacy and safety of intranasal sufentanil/midazolam [S/M] and ketamine/madazolam [K/M] for sedation and analgesia in preschool children that require dental surgery [extractions].<br /> <br /> Fifty children [ASA 1] aged 5 &ndash / 7 years, requiring six or more dental extractions under general anaesthesia, were allocated to two groups of 25 children to receive either ketamine 5 mg/kg or sufentanil 20&mu / g intranasally, 20 minutes before induction of surgery in this randomised double-blind study. All the children in both groups in addition concurrently received nasal midazolam 0,3 mg/kg. For induction of anaesthesia, sevoflurane in nitrous oxide and oxygen, was used.<br /> <br /> S/M was accepted significantly better as a nasal pre-medication [p&lt / 0.05]. Both groups were equally sedated and a smooth mask induction of anaesthesia was experienced in the majority of children. Recovery of children in both groups were similar / 82% of the S/M group were fully recovered 120 minutes post-operatively versus 80% in the K/M group [p&gt / 0,05]. Effective postoperative analgesia for multiple extractions was provided. For pain evaluation, children were divided into two groups, a non-responder group where all pain values over time were more than 40 and a responder group where pain values were equal to, or less than 40. Seventy two percent of children in the S/M group were responders as to fifty two percent in the K/M group [p&gt / 0,05]. No adverse respiratory, cardiovascular or other effects were recorded. This study showed that intranasal administration of sufentanil /midazolam or ketamine/midazolam, provides safe and effective sedation and analgesia in children aged 5&ndash / 7 years undergoing multiple dental extractions.

<p>This thesis covered the fast track assessment of the referred dental patient for conscious sedation in a day clinic. The assessment took in consideration patient information, medical history, anatomical observations, treatment required, phobic aspects and patient expectations.</p>

Intravenous administration of benzodiazepines can be used for anxiety management in dentistry. The recent approval of Dexmedetomidine in Canada provides an alternative to benzodiazepines for moderate sedation. There is no review comparing Dexmedetomidine and Midazolam as a sole agent for intravenous moderate sedation. This paper determines to fill the void of knowledge. A total of 6 articles out of 117 were identified in Pubmed and Ovid Medline using the key terms “Dexmedetomidine” and “sedation”. The parameters that were evaluated were the need for rescue, patient and surgeon satisfaction, and adverse outcomes. Dexmedetomidine was found to be equal or better than Midazolam in the first three parameters. Hypotension and bradycardia were evident in moderate to high doses, but none needing intervention. Other side effects include headache and dry mouth. Dexmedetomidine is a reasonable and safe alternative to Midazolam, but more research is needed to evaluate Dexmedetomidine for general dentistry.

This study investigated Ontario dentists' views and use of sedation and general anaesthesia (GA) (n=1076; 37.9% response rate). A mixed mode format offered mailed and web survey options. Study participants were 69.7% male, 83.0% general practitioners, practicing 0.5-42 years (mean 20.6 years), with 40.6% from cities &gt;500,000. 60.2% of respondents provided sedation. Dentists' underestimated patient interest in sedation/GA (66.8% vs. 43.9% not interested; 19.8% vs. 42.8% possibly interested; 13.4% vs. 12.4% definitely interested). Patients' preference for sedation/GA by service was also underestimated (p&lt;0.001) except for extractions. Barriers to care were cost (72.2%) for providers; lack of training (38.2%) and patient demand (25.3%) for non-providers. Dentists reported use of sedation highest for extractions (1.5% deep sedation/GA-5.7% nitrous). Dentists' also overestimated patients' level of fear (somewhat afraid 19.95 vs. 9.8%; very afraid 10.6% vs. 2.0%; terrified 6.0% vs. 3.5%). This study confirms differences between dentists' use and estimation of patient demand for sedation/GA.

<p>The purpose of this research project was to assess the safety and efficacy of a combination of drugs for conscious sedation in patients undergoing office-based plastic and reconstructive surgery. A pilot study was done to determine the safety of the co-administration of the drugs used in the sedation technique.</p>

Intravenous administration of benzodiazepines can be used for anxiety management in dentistry. The recent approval of Dexmedetomidine in Canada provides an alternative to benzodiazepines for moderate sedation. There is no review comparing Dexmedetomidine and Midazolam as a sole agent for intravenous moderate sedation. This paper determines to fill the void of knowledge. A total of 6 articles out of 117 were identified in Pubmed and Ovid Medline using the key terms “Dexmedetomidine” and “sedation”. The parameters that were evaluated were the need for rescue, patient and surgeon satisfaction, and adverse outcomes. Dexmedetomidine was found to be equal or better than Midazolam in the first three parameters. Hypotension and bradycardia were evident in moderate to high doses, but none needing intervention. Other side effects include headache and dry mouth. Dexmedetomidine is a reasonable and safe alternative to Midazolam, but more research is needed to evaluate Dexmedetomidine for general dentistry.

This study investigated Ontario dentists' views and use of sedation and general anaesthesia (GA) (n=1076; 37.9% response rate). A mixed mode format offered mailed and web survey options. Study participants were 69.7% male, 83.0% general practitioners, practicing 0.5-42 years (mean 20.6 years), with 40.6% from cities &gt;500,000. 60.2% of respondents provided sedation. Dentists' underestimated patient interest in sedation/GA (66.8% vs. 43.9% not interested; 19.8% vs. 42.8% possibly interested; 13.4% vs. 12.4% definitely interested). Patients' preference for sedation/GA by service was also underestimated (p&lt;0.001) except for extractions. Barriers to care were cost (72.2%) for providers; lack of training (38.2%) and patient demand (25.3%) for non-providers. Dentists reported use of sedation highest for extractions (1.5% deep sedation/GA-5.7% nitrous). Dentists' also overestimated patients' level of fear (somewhat afraid 19.95 vs. 9.8%; very afraid 10.6% vs. 2.0%; terrified 6.0% vs. 3.5%). This study confirms differences between dentists' use and estimation of patient demand for sedation/GA.