Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults.

STUDY OBJECTIVE: We compare intranasal ketamine with intranasal placebo in providing pain reduction at 30 minutes when added to usual paramedic care with nitrous oxide. METHODS: This was a randomized double-blind study of out-of-hospital patients with acute pain who reported a verbal numeric rating scale (VNRS) pain score greater than or equal to 5. Exclusion criteria were younger than 18 years, known ketamine intolerance, nontraumatic chest pain, altered mental status, pregnancy, and nasal occlusion. Patients received usual paramedic care and were randomized to receive either intranasal ketamine or intranasal saline solution at 0.75 mg/kg. The primary outcome was the proportion of patients with VNRS score reduction greater than or equal to 2 at 30 minutes. Secondary outcomes were pain reduction at 15 minutes, patient-reported comfort, satisfaction scores, nitrous oxide consumption, and incidence of adverse events. RESULTS: One hundred twenty subjects were enrolled. Seventy-six percent of intranasal ketamine patients versus 41% of placebo patients reported a greater than or equal to 2-point VNRS reduction at 30 minutes (difference 35%; 95% confidence interval 17% to 51%). Median VNRS reduction at 15 minutes was 2.0 and 1.0 and at 30 minutes was 3.0 and 1.0 for ketamine and placebo, respectively. Improved comfort at 15 and 30 minutes was reported for 75% versus 57% and 61% versus 46% of ketamine and placebo patients, respectively. Sixty-two percent of patients (95% confidence interval 49% to 73%) versus 20% (95% confidence interval 12% to 32%) reported adverse events with ketamine and placebo, respectively. Adverse events were minor, with no patients requiring physical or medical intervention. CONCLUSION: Added to nitrous oxide, intranasal ketamine provides clinically significant pain reduction and improved comfort compared with intranasal placebo, with more minor adverse events.

Intranasal ketamine for analgesia in the emergency department: a prospective observational series.

OBJECTIVES: The objective was to examine the feasibility, effectiveness, and adverse effect profile of intranasal ketamine for analgesia in emergency department (ED) patients. METHODS: This was a prospective observational study examining a convenience sample of patients aged older than 6 years experiencing moderate or severe pain, defined as a visual analog scale (VAS) score of 50 mm or greater. Patients received 0.5 to 0.75 mg/kg intranasal ketamine. Pain scores were recorded on a standard 100-mm VAS by trained investigators at baseline, then every 5 minutes for 30 minutes, and then every 10 minutes for an additional 30 minutes. The primary outcome was the number and proportion of patients experiencing clinically significant reductions in VAS pain scores, defined as VAS reductions of 13 mm or more, within 30 minutes. Secondary outcomes included the median reduction in VAS, the median time required to achieve a 13 mm reduction in VAS, vital sign changes, and adverse events. Continuous data are reported with medians and interquartile ranges (IQRs). The Wilcoxon signed-ranks test was used to assess changes in VAS scores. Adverse effects are reported with proportions and 95% confidence intervals (CIs). RESULTS: Forty patients were enrolled with a median age of 47 years (IQR = 36 to 57 years; range = 11 to 79 years) for primarily orthopedic injuries. A reduction in VAS of 13 mm or more within 30 minutes was achieved in 35 patients (88%). The median change in VAS at 30 minutes was 34 mm (44%). Median time required to achieve a 13 mm VAS reduction was 9.5 minutes (IQR = 5 to 13 minutes; range = 5 to 25 minutes). No serious adverse effects occurred. Minor adverse effects included dizziness (21 patients, 53%; 95% CI = 38% to 67%), feeling of unreality (14 patients, 35%; 95% CI = 22% to 50%), nausea (four patients, 10%; 95% CI = 4% to 23%), mood change (three patients, 8%; 95% CI = 3% to 20%), and changes in hearing (one patient, 3%; 95% CI = 0% to 13%). All adverse effects were transient and none required intervention. There were no changes in vital signs requiring clinical intervention. CONCLUSIONS: Intranasal ketamine reduced VAS pain scores to a clinically significant degree in 88% of ED patients in this series. Adverse effects were minor and transient. Intranasal ketamine may have a role in the provision of effective, expeditious analgesia to ED patients.

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.

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.

A prospective evaluation of "ketofol" (ketamine/propofol combination) for procedural sedation and analgesia in the emergency department.

STUDY OBJECTIVE: We evaluate the effectiveness and consider the safety of intravenous ketamine/propofol combination ("ketofol") in the same syringe for procedural sedation and analgesia in the emergency department (ED). METHODS: A prospective case series of consecutive ketofol procedural sedation and analgesia events in the ED of a trauma-receiving community teaching hospital from July 2005 to February 2006 was studied. Patients of all ages, with any comorbid conditions, were included. Ketofol (1:1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was administered intravenously at the discretion of the treating physician by using titrated aliquots. The presence or absence of adverse events was documented, as were procedural success, recovery time, and physician, nurse, and patient satisfaction. Physiologic data were recorded with established hospital procedural sedation and analgesia guidelines. RESULTS: One hundred fourteen procedural sedation and analgesia events using ketofol were performed for primarily orthopedic procedures. The median dose of medication administered was ketamine at 0.75 mg/kg and propofol at 0.75 mg/kg (range 0.2 to 2.05 mg/kg each of propofol and ketamine; interquartile range [IQR] 0.6 to 1.0 mg/kg). Procedures were successfully performed without adjunctive sedatives in 110 (96.5%) patients. Three patients (2.6%; 95% confidence interval [CI] 0.6% to 7.5%) had transient hypoxia; of these, 1 (0.9%; 95% CI 0.02% to 4.8%) required bag-valve-mask ventilation. Four patients (3.5%; 95% CI 1.0% to 8.7%) required repositioning for airway malalignment, 4 patients (3.5%; 95% CI 1.0% to 8.7%) required adjunctive medication for sedation, and 3 patients (2.6%; 95% CI 0.6% to 7.5%) had mild unpleasant emergence, of whom 1 (0.9%; 95% CI 0.02% to 4.8%) received midazolam. No patient had hypotension or vomiting or received endotracheal intubation. Median recovery time was 15 minutes (range 5 to 45 minutes; IQR 12 to 19 minutes). Median physician, nurse, and patient satisfaction scores were 10 on a 1-to-10 scale. CONCLUSION: Ketofol procedural sedation and analgesia is effective and appears to be safe for painful procedures in the ED. Few adverse events occurred and were either self-limited or responded to minimal interventions. Recoveries were rapid, and staff and patients were highly satisfied.