Table 6.
Conclusions on Safety and Efficacy of the Included Reviews
| Sedative Agent Review, Year of Publication (Indications for Sedation Included in Review) | Safety (+/−) | Efficacy (+/−) | Summary of Conclusions (With Respect to the Agents for Procedural Sedation in Children) |
|---|---|---|---|
| Ketamine | |||
| Deasy 20109 (any procedural sedation) | + | + | IV ketamine appears to have a better AE profile and ashorter recovery period. IV ketamine should be administered if access is available or if staff is skilled at initiating IV access. IM administration may be preferable if IV access is difficult. Brief procedures are believed to have the best recovery from IV administration. |
| NICE 201020 (painful or nonpainful diagnostic or therapeutic procedures) | + | + | IV and IM ketamine were shown to be equally effective. Smaller doses may be titrated via IV, which reduces the chance of sedation outlasting the procedure. Compared with midazolam‐fentanyl, ketamine‐midazolam was associated with lower pain and distress scores. Similar results were found for comparisons with propofol‐fentanyl, although ketamine‐midazolam had longer recovery time. Ketamine‐midazolam was associated with fewer oxygen desaturations in both comparisons. |
| Green 200910, 11 (any procedural sedation) | + | NA | Risk factors for ketamine‐associated AEs are high IV doses, administration to children aged <2 or >13 years, and the use of coadministered anticholinergics or benzodiazepines. Risks are not altered by route, oropharyngeal procedures, or underlying physical illness. Risk factors for any recovery agitation are low IM dose and unusually highIV dose, with no important risk factors for clinically important recovery agitation. The data did not support the regular or routine use of anticholinergics or benzodiazepines. |
| Migita 200612 (fracture reduction) | + | + | Ketamine was found to be the most effective of the parenteral treatments examined, although it has consistently longer recovery times than other agents. Ketamine‐midazolam therapy is associated with fewer AEs than other parenteral drug combinations. |
| Mistry 200514 (any conscious sedation) | + | + | Compared with traditional agents, ketamine is an effective agent with minimal AEs and sequelae. Administration via IV and IM routes are considered equally safe. However, administering physicians should be adequately trained in the use of ketamine and in airway management and resuscitation. Additionally, sufficient support personnel are required for patient management. |
| Howes 200415 (any painful procedure) | + | NA | Ketamine is safe and acceptable. Rare occurrences of serious AEs require experienced staff skilled in advanced airway maintenance, with adequate monitoring and resuscitation equipment available. |
| Mace 200417 (any painful procedure) | + | + | For brief, painful procedures ketamine is effective as a sole agent or in combination with a benzodiazepine. Ketamine can be safely used, but may require head positioning, supplemental oxygen, occasional bag‐valve‐mask ventilatory support, and measures to address laryngospasm. The addition of midazolam to ketamine does not decrease the incidence of emergent reactions, but does decrease the incidence of emesis. |
| Midazolam | |||
| Jameson 20117 (simple lacerations requiring suturing) | NA | − | In a comparison of midazolam versus ketamine, ketamine was recommended as sedative of choice as it offers quick, reliable sedation with minimal AEs and has rapid onset and offset time. Ketamine can be delivered via IM if venous access is difficult. |
| Leroy 201019 (any procedural sedation) | − | NA | During PS and its subsequent recovery phase the use of benzodiazepines, chloral hydrate, barbiturates, opiates, or combinations of these medicines pose a variable risk of potentially serious AEs, especially for respiratory depression and/or airway obstruction. For medicines such as chloral hydrate, midazolam, barbiturates, opiates, or combinations, the depth of sedation, effectiveness and duration of sedation, and timing of AEs cannot be reliably predicted. |
| NICE 201020 (painful or nonpainful diagnostic or therapeutic procedures) | + (alone) − (combination) | − (alone) + (combination) | Midazolam was the most common sedative investigated; however, it is probably not an effective sedative drug on its own and can be combined with fentanyl, ketamine, propofol, or NO. When doses are limited, midazolam alone had a good safety profile. In combination with ketamine, NO, or opioids, midazolam can produce deep sedation, which may result in harms; therefore, the AEs of multidrug sedation should be weighed against the benefit of pain relief for a procedure. |
| Mace 200417 (any painful procedure) | − | + | Fentanyl and midazolam are effective agents. The efficacy of IV fentanyl and midazolam ranges from 91% to 100%, which is similar to alternative agents. The analgesic and sedative effects of fentanyl may be increased when combined with a benzodiazepine. The combination of fentanyl and midazolam appears to have a greater risk of respiratory depression; therefore, clinicians should monitor patients for signs of respiratory depression and have appropriate training and support to treat apnea. |
| Nitrous oxide | |||
| Pedersen 201316 (brief, painful minor procedures) | + | + (not equal for all children) | For minor painful procedures NO is a safe and effective method to use to achieve sedation. Onset is rapid, quickly reversible, does not have major AEs, and can be safely administered by a dedicated staff member trained in basic airway management. NO is not equally effective for all children, and another method of pain management should be prepared in case of treatment failure. |
| Leroy 201019 (any procedural sedation) | + | NA | NO is associated with an extremely low chance of serious AEs. Risks include: 1) <1 year old and 2) simultaneous use of other sedatives. No significant difference in median fasting time between patients with and without emesis was found. NO 70% causes significantly deeper sedation compared to NO 50%; however, there is no significant difference in AE rates between regimens. |
| NICE 201020 (painful or nonpainful diagnostic or therapeutic procedures) | + | + | NO was not found to be more effective than oxygen alone in young uncooperative children; however, when children were cooperative NO provided sufficient analgesia in a wide range of painful procedures. Overall, NO was well tolerated, short acting, and highly effective in selected patient groups and settings. Occasional AEs include dysphoria and vomiting, but this may be related to higher concentrations. |
| Migita 200612 (fracture reduction) | ? | ? | Data are too limited to support this intervention's effectiveness or to make conclusions on its safety. NO does, however, have significantly shorter treatment times than other modalities. |
| Faddy 200513 (any procedural sedation) | + | + | Previously, NO 50% has been shown to have similar efficacy for pain relief compared to IV administered conventional analgesia including opioid analgesia. Side effects are uncommon and AEs (hypotension, oxygen desaturation) could not be attributed to NO inhalation. Recovery from sedative effects of NO is faster compared with IV analgesia. The side effect profile of this agent suggests that it could be used safely by adequately trained lay persons in the prehospital setting. NO 50% is an effective and safe form of analgesia. |
| Propofol | |||
| Lamond 20108 (any procedural sedation) | + | NA | Propofol used for procedural sedation is associated with a low risk of minor AEs. Confounding variables that influence the likelihood of these events include: adjunct opiates, propofol dosing strategies, and supplemental oxygen. Minor AEs for propofol are similar to those found for other ED sedation agents. Capnography provides useful clinical feedback about impending hypoventilation and apnea. Therefore, AE data for pediatric propofol sedation supports its ongoing use in the ED. |
| Leroy 201019 (any procedural sedation) | − | NA | Use of propofol for PS presents a real risk of potentially serious AEs, especially respiratory depression and/or airway obstruction. PS with propofol is equally safe when conducted by anesthesiologists versus nonanesthesiologists if the latter are well trained and part of a dedicated sedation team. |
| Mace 201017 (any painful procedure) | + | + | Propofol combined with opiate agents is effective in producing cooperation for painful procedures, as is propofol when given alone. Propofol is safe when given in combination with opiates and alone, but may require head positioning, supplemental oxygen, and occasional bag‐valve‐mask ventilatory support. |
| NICE 201020 (painful or nonpainful diagnostic or therapeutic procedures) | – | + | Propofol can be titrated to achieve any level of sedation. In comparison to other drug combinations, unconsciousness and airway effects are more likely with propofol, but are brief. Recovery after propofol is more rapid and airway obstruction or apnea can be managed with appropriate skills and equipment. |
| Migita 200612 (fracture reduction) | − | − | Propofol is not as effective as ketamine therapy and is associated with more AEs, particularly respiratory events and hypotension than other parental agents. Recovery time and total sedation time are shorter with propofol than other treatment modalities. |
| Symington 200618 (any procedural sedation) | + | + | Propofol can be used safely and effectively in the ED. Many studies appear to use deep sedation or general anesthesia, which is not recommended for nonanesthetists in the United Kingdom, and could be considered dangerous when patients are not fasted or fully prepared preprocedure. |
AE = adverse event; IM = intramuscular; IV = intravenous; NA = not analyzed; NO = nitrous oxide; PS = procedural sedation.