Alterations in haemodynamic parameters during procedural sedation and analgesia in children: Is ketamine really to blame?

It is with great interest that we read ‘ketamine may be related to reduced ejection fraction in children during procedural sedation’ by Eken et al. ¹ At our institution, we run a procedural sedation and analgesia (PSA) service, and we have performed more than 10,000 procedures on children over the last 6 years. The vast majority of these cases are outpatients. One of the medications commonly used is ketamine in conjunction with other sedative and analgesic agents which allows us to reduce the dose of all medications, hence their potentially adverse events while maintaining spontaneous breathing in children. Adverse events do occur although rarely and they are of respiratory origin in particular. We are surprised by the significant differences between the results derived from this cohort study with both our experience and recent data from literature, suggesting that other reasons could have caused alterations in haemodynamic parameters rather than solely ketamine.

It is undeniable that children belong to a population group who are prone to adverse events during PSA. All currently used sedatives aim to depress awareness, and in doing so, they may potentially inhibit centrally mediated haemodynamic control particularly with increasing doses.

Ketamine is an N-methyl-d-aspartate receptor antagonist that blocks glutamate in the limbic system. However, the mechanism of receptor blockade differs based on ketamine concentration. While at low concentrations, analgesic properties are evident; at higher concentrations, ketamine causes an anaesthetic state called ‘dissociative anaesthesia’ as a result of a functional dissociation between the cortical and limbic systems. ² Assuming large doses are not rapidly administered, ketamine may preserve pharyngeal and laryngeal protective reflexes, lowers airway resistance, increases lung compliance and is less likely to induce respiratory depression. Furthermore, unlike other sedatives, ketamine is sympathomimetic and facilitates adrenergic transmission, which offsets its direct myocardial depressant actions. It also increases the systemic catecholamine concentrations by centrally mediated release of catecholamine and inhibition of neuronal catecholamine reuptake which is expected to result in an increased heart rate and blood pressure, hence maintaining haemodynamic stability in critically ill patients. ³ This unique pharmacodynamic profile of ketamine makes it an appealing alternative agent for PSA overall within the paediatric population ⁴ and in the emergency department (ED). ⁵ However, like all drugs, ketamine is not without side effects, and a ‘single, safe and effective’ agent for paediatric PSA is yet to be determined. With increasing doses, ketamine may induce laryngospasm, respiratory depression, hypersalivation, emesis and emergence phenomena.

ED is a clearly different situation where procedures performed are likely to be painful and urgent in nature, yet safety concerns while using ketamine in this setting still remain real. In their manuscript, the authors described haemodynamic changes based on blood pressure and echocardiography findings. However, measuring blood pressure and performing echocardiography prior to sedation on injured, painful and agitated small children who are admitted to a stressful environment of ED particularly following the establishment of an intravenous access may be challenging, and it raises the question of accuracy in both the definition of a normal blood pressure and standardization of measuring it in these situations as well as the provided high-quality scanning windows while performing echocardiography. Both may lead to overestimation of blood pressure and underestimation of left ventricular ejection fraction. A proper PSA approach probably normalizes the blood pressure in these children rather than decreasing it significantly. When ketamine is used, clinical practice demonstrates both an increased systolic function and an increased afterload condition through its sympathomimetic actions. The contradictory findings from this report could be explained by the methodology wherein the authors have utilized a unidimensional method (M mode) to determine the volume of the left ventricle. More optimal would have been to estimate the fractional area contraction, which is based on the two-dimensional images (end diastolic and end systolic area of the left ventricle), ⁶ which provide fairly comparable values with invasive ventriculography. On the contrary, fractional shortening is obtained from M mode that traditionally offers low values, owing to the unidimensional approach. In addition, small sample size and lack of statistically significant and clinically relevant data make it difficult (if possible at all) to draw and generalize the conclusion taken from this cohort.

Taken as a whole, in experienced hands, paediatric PSA produced by ketamine may be associated with few cardiopulmonary adverse events and clinically insignificant systemic haemodynamic changes. Therefore, we suggest gradual dose titration with careful monitoring when using ketamine in well-selected children, and we believe that ketamine should not be abandoned in settings where pain and stress have become an issue in children.