Gary Andolfatto

A Prospective Case Series of Pediatric Procedural Sedation and Analgesia in the Emergency Department Using Single-syringe Ketamine–Propofol Combination (Ketofol)

OBJECTIVES This study evaluated the effectiveness, recovery time, and adverse event profile of intravenous (IV) ketofol (mixed 1:1 ketamine-propofol) for emergency department (ED) procedural sedation and analgesia (PSA) in children. METHODS Prospective data were collected on all PSA events in a trauma-receiving, community teaching hospital over a 3.5-year period, from which data on all patients under 21 years of age were studied. Patients receiving a single-syringe 1:1 mixture of 10 mg/mL ketamine and 10 mg/mL propofol (ketofol) were analyzed. Patients received ketofol in titrated aliquots at the discretion of the treating physician. Effectiveness, recovery time, caregiver and patient satisfaction, drug doses, physiologic data, and adverse events were recorded. RESULTS Ketofol PSA was performed in 219 patients with a median age of 13 years (range = 1 to 20 years; interquartile range [IQR] = 8 to 16 years) for primarily orthopedic procedures. The median dose of medication administered was 0.8 mg/kg each of ketamine and propofol (range = 0.2 to 3.0 mg/kg; IQR = 0.7 to 1.0 mg/kg). Sedation was effective in all patients. Three patients (1.4%; 95% confidence interval [CI] = 0.0% to 3.0%) had airway events requiring intervention, of which one (0.4%; 95% CI = 0.0% to 1.2%) required positive pressure ventilation. Two patients (0.9%; 95% CI = 0.0% to 2.2%) had unpleasant emergence requiring treatment. All other adverse events were minor. Median recovery time was 14 minutes (range = 3 to 41 minutes; IQR = 11 to 18 minutes). Median staff satisfaction was 10 on a 1-to-10 scale. CONCLUSIONS Pediatric PSA using ketofol is highly effective. Recovery times were short; adverse events were few; and patients, caregivers, and staff were highly satisfied.

Ketamine-Propofol Combination (Ketofol) Versus Propofol Alone for Emergency Department Procedural Sedation and Analgesia: A Randomized Double-Blind Trial

STUDY OBJECTIVE We determine whether a 1:1 mixture of ketamine and propofol (ketofol) for emergency department (ED) procedural sedation results in a 13% or more absolute reduction in adverse respiratory events compared with propofol alone. METHODS Participants were randomized to receive either ketofol or propofol in a double-blind fashion. Inclusion criteria were aged 14 years or older and American Society of Anesthesiology class 1 to 3 status. The primary outcome was the number and proportion of patients experiencing an adverse respiratory event as defined by the Quebec Criteria. Secondary outcomes were sedation consistency, efficacy, and time; induction time; and adverse events. RESULTS A total of 284 patients were enrolled, 142 per group. Forty-three (30%) patients experienced an adverse respiratory event in the ketofol group compared with 46 (32%) in the propofol group (difference 2%; 95% confidence interval -9% to 13%; P=.80). Three ketofol patients and 1 propofol patient received bag-valve-mask ventilation. Sixty-five (46%) patients receiving ketofol and 93 (65%) patients receiving propofol required repeated medication dosing or progressed to a Ramsay Sedation Score of 4 or less during their procedure (difference 19%; 95% confidence interval 8% to 31%; P=.001). Six patients receiving ketofol were treated for recovery agitation. Other secondary outcomes were similar between the groups. Patients and staff were highly satisfied with both agents. CONCLUSION Ketofol for ED procedural sedation does not result in a reduced incidence of adverse respiratory events compared with propofol alone. Induction time, efficacy, and sedation time were similar; however, sedation depth appeared to be more consistent with ketofol.

A prospective case series of single-syringe ketamine-propofol (Ketofol) for emergency department procedural sedation and analgesia in adults.

OBJECTIVES The objective was to evaluate the effectiveness, recovery time, and adverse event profile of intravenous (IV) mixed 1:1 ketamine-propofol (ketofol) for adult procedural sedation and analgesia (PSA) in the emergency department (ED). METHODS   Prospective data were collected on all PSA events over a 4.5-year period in a trauma-receiving suburban teaching hospital. PSAs using a 1:1 single-syringe mixture of 10 mg/mL ketamine and 10 mg/mL propofol in patients over 21 years of age were analyzed. Physiologic data, drug doses, adverse events, recovery time, patient satisfaction, and staff satisfaction were recorded. RESULTS Ketofol PSA was used in 728 patients for primarily orthopedic procedures. Median patient age was 53 years (range = 21 to 99 years, interquartile range [IQR] = 36-70 years). The median dose of ketamine and propofol was 0.7 mg/kg each (range =0.2 to 2.7 mg/kg, IQR = 0.5-0.9 mg/kg), and median recovery time was 14 minutes (range = 3 to 50 minutes, IQR = 10-17 minutes). PSA was effective in 717 cases (98%). Bag-mask ventilation occurred in 15 patients (2.1%; 95% confidence interval [CI] = 1.0% to 3.1%). Recovery agitation occurred in 26 patients (3.6%; 95% CI = 2.2% to 4.9%), of whom 13 (1.8%; 95% CI = 0.8% to 2.7%) required treatment. One patient experienced vomiting and one patient was admitted to the hospital for monitoring of transient dysrhythmia and hypotension. No sequelae were identified. The median staff satisfaction scores were 10 (IQR = 9-10) on a scale of 1 to 10, and 97% of patients would have chosen the same method of PSA in the future. CONCLUSIONS   Ketofol is an effective PSA agent in adult ED patients. Recovery times are short and adverse events are few. Patients and ED staff were highly satisfied.

Ketamine: use in anesthesia.

The role of ketamine anesthesia in the prehospital, emergency department and operating theater settings is not well defined. A nonsystematic review of ketamine was performed by authors from Australia, Europe, and North America. Results were discussed among authors and the final manuscript accepted. Ketamine is a useful agent for induction of anesthesia, procedural sedation, and analgesia. Its properties are appealing in many awkward clinical scenarios. Practitioners need to be cognizant of its side effects and limitations.

Ketofol for Procedural Sedation? Pro and Con

In an old Reese’s Peanut Butter Cups television commercial, 2 snacking pedestrians collide and their respective treats—peanut butter and chocolate—inadvertently mix. Both parties sample the blend with unexpected pleasure, and the narrator then pitches the slogan, “Two great tastes that taste great together.” Ketamine and propofol are 2 extremely common agents used for emergency department (ED) procedural sedation, with each having well-documented safety and efficacy. But do these 2 drugs work better together? The combination of ketamine and propofol, referred to by the portmanteau “ketofol,” is currently all the rage. According to Internet and physician buzz, a large number of EDs in North America have adopted this combination as their primary sedation regimen. Much of this popularity has been fueled by anecdote rather than solid research. This is reminiscent of the dramatic entry of propofol a decade ago into emergency medicine, in which clinical application surged far ahead of the science. Ultimately, the original enthusiasm for propofol was properly validated, but will ketofol enjoy the same outcome? Other popular anecdotal therapies were later discredited, eg, aminophylline for asthma, antishock trousers for traumatic hypotension, highdose epinephrine in cardiac arrest. The concept of ketofol has immediate allure because of its intriguing synergistic premise. These 2 completely different sedatives exhibit clinical features that appear to balance each other’s deficits. Propofol is a superb sedative but lacks the analgesia that ketamine can amply provide. Respiratory depression and hypotension are the principal adverse events of propofol; perhaps the sympathomimetic ketamine mitigates them. Vomiting and hallucinatory recovery reactions are the principal adverse events of ketamine; perhaps the antiemetic and hypnotic properties of propofol mitigate them. In this editorial, we debate the pros and cons of ketofol, with our preexisting biases against (S.M.G.), for (G.A.), and neutral (B.K.). Summary arguments are show in the Figure. h

Ketamine and Intracranial Pressure: No Contraindication Except Hydrocephalus

Shortly after the 1970 introduction of ketamine, there appeared multiple worrisome reports of elevated intracranial pressure (Figure). Many of the cited intracranial pressure values were significant—the largest increase was 1,600 mm H2O 9 —and alarming sequelae included apnea and bradycardia. Anesthesiologists quickly abandoned ketamine in patients with neurologic disorders, and a contraindication in settings of possible intracranial pressure elevation subsequently appeared in anesthesiology textbooks and review articles, including patients with cerebral trauma, mass, or hemorrhage. Two decades later when ketamine revolutionized emergency department pediatric procedural sedation, this established contraindication was assumed to apply and was dutifully reproduced in emergency medicine reviews and textbooks. Emergency physicians were fearful to use ketamine in disease states or for procedures with the potential for increased intracranial pressure, including lumbar puncture for suspected meningitis and rapid sequence intubation for trauma. This sequence of events illustrates how clinical maxims can be quickly formed and promulgated and become dogma despite incomplete evidence, and how when such mandates are misguided it can take decades of research efforts and handwringing to reverse them. During these corrective periods, patients may be deprived of effective treatment options. In hindsight, the well-intentioned 1970s anesthesiologists who encouraged this edict made 2 critical errors. First, it should have been recognized that the largest intracranial pressure elevations and all occurrences of sequelae requiring intervention occurred in patients with preexisting hydrocephalus (Figure). Among these patients, those with intact cerebrospinal fluid flow tolerated intracranial pressure increases without incident, as would be expected. Second, as early as 1972 it was recognized that ketamine increases intracranial blood flow through cerebral vasodilation, and despite absolute increases in intracranial pressure cerebral perfusion is maintained or improved. These factors should have mitigated the concerns and prevented the extrapolation of the ketamine contraindication beyond those

Ketofol for Procedural Sedation Revisited: Pro and Con

Ketamine andpropofol are both core emergency department (ED) procedural sedation agents. Their concurrent administration—referred to by the portmanteau “ketofol”— is widespread and based on an alluring premise of synergy. Ketamine is sympathomimetic and could theoretically mitigate propofol-associated respiratory depression and hypotension. Propofol is a sedative with antiemetic properties and could hypothetically counter the ketamineassociated recovery agitation and emesis. Furthermore, ketamine adds analgesia to the purely sedative action of propofol. In 2011, we debated the merits of the ketofol combination. Subsequently, 2 large, well-designed, randomized, controlled trials have provided compelling evidence on which to substantively advance this discussion.We therefore update these pro and con positions, with our preexisting biases against (S.M.G.), for (G.A.), and neutral (B.S.K.). Summary arguments are show in the Figure.

Prevalence of alcohol and drug use in injured British Columbia drivers

Objectives Determine the prevalence of drug use in injured drivers and identify associated demographic factors and crash characteristics. Design Prospective cross-sectional study. Setting Seven trauma centres in British Columbia, Canada (2010–2012). Participants Automobile drivers who had blood obtained within 6 h of a crash. Main outcome measures We analysed blood for cannabis, alcohol and other impairing drugs using liquid chromatography/mass spectrometry (LCMS). Results 1097 drivers met inclusion criteria. 60% were aged 20–50 years, 63.2% were male and 29.0% were admitted to hospital. We found alcohol in 17.8% (15.6% to 20.1%) of drivers. Cannabis was the second most common recreational drug: cannabis metabolites were present in 12.6% (10.7% to 14.7%) of drivers and we detected Δ-9-tetrahydrocannabinol (Δ-9-THC) in 7.3% (5.9% to 9.0%), indicating recent use. Males and drivers aged under 30 years were most likely to use cannabis. We detected cocaine in 2.8% (2.0% to 4.0%) of drivers and amphetamines in 1.2% (0.7% to 2.0%). We also found medications including benzodiazepines (4.0% (2.9% to 5.3%)), antidepressants (6.5% (5.2% to 8.1%)) and diphenhydramine (4.7% (3.5% to 6.2%)). Drivers aged over 50 years and those requiring hospital admission were most likely to have used medications. Overall, 40.1% (37.2% to 43.0%) of drivers tested positive for alcohol or at least one impairing drug and 12.7% (10.7% to 14.7%) tested positive for more than one substance. Conclusions Alcohol, cannabis and a broad range of other impairing drugs are commonly detected in injured drivers. Alcohol is well known to cause crashes, but further research is needed to determine the impact of other drug use, including drug–alcohol and drug–drug combinations, on crash risk. In particular, more work is needed to understand the role of medications in causing crashes to guide driver education programmes and improve public safety.

Does the sedation regimen affect adverse events during procedural sedation and analgesia in injection drug users

OBJECTIVES Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) as part of emergency department (ED) treatment. We compared adverse events (AEs) using a variety of sedation regimens. METHODS This was a retrospective analysis of a PSA safety audit in two urban EDs. Consecutive self-reported IDUs were identified, and structured data describing comorbidities, vital signs, sedation regimens (propofol [P], propofol-fentanyl [PF], fentanyl-midazolam [FM], ketofol [1:1 ketamine:propofol, KF], and ketamine-propofol [KP]) and AEs were collected. The primary outcome was the proportion of patients in each sedation group having an AE; the secondary outcome was the proportion of patients having a cardiovascular or respiratory AE. RESULTS Data were collected on 276 IDUs (78 P, 82 PF, 65 FM, 25 KF, and 26 KP), and 18 patients had AEs (6.5%, 95% CI 4.0-10.3). The AE rates were 0.0%, 8.5%, 9.2%, 12.0%, and 7.6%, respectively, with propofol having a significantly lower rate (Pearson coefficient 14.9, p  =  0.007). The cardiovascular/respiratory AE rates were significantly different as well, with P, KP, and KF having the lowest rates (Pearson coefficient 13.3, p  =  0.01). CONCLUSIONS For IDU PSA, the overall AE rate was 6.5%, and propofol appeared to have a significantly lower rate.

Do injection drug users have more adverse events during procedural sedation and analgesia for incision and drainage of cutaneous abscesses

OBJECTIVE Injection drug users (IDUs) often undergo procedural sedation and analgesia (PSA) in the emergency department (ED). We compared adverse events (AEs) for IDUs to those for non-IDUs receiving PSA for incision and drainage of cutaneous abscesses. METHODS This was a retrospective analysis of a PSA safety audit. IDU status was prospectively documented among consecutive patients undergoing PSA at two urban EDs. Structured data describing comorbidities, vital signs, sedation regimens, and adverse events were collected. Primary outcome was the proportion of patients in each group experiencing an AE, whereas the secondary outcomes included recovery times. RESULTS Of 525 consecutive patients receiving PSA for incision and drainage of an abscess, 244 were deemed IDUs and 281 non-IDUs. IDUs received higher doses of sedatives and analgesics, and 14 experienced AEs (5.7%), whereas 10 non-IDUs had AEs (3.6%), for a risk difference of 2.1% (95% CI -1.8, 6.5). Median recovery times were 18 minutes (interquartile range [IQR] 10-36) for IDUs and 12 minutes (IQR 7-19) for non-IDUs, for a difference of 6 minutes (95% CI 2-9 minutes). Median sedation times were also longer in IDUs, for a difference of 6 minutes (95% CI 5-10 minutes). Of 20 IDU patients and 1 non-IDU patient admitted to hospital, none had experienced an AE related to PSA. CONCLUSIONS For ED patients requiring PSA for incision and drainage, IDUs had an AE rate similar to that of non-IDUs but longer sedation and recovery times. In experienced hands, PSA may be as safe in IDUs as in patients who do not use injection drugs.