The safety and utility of pediatric epidural analgesia is well established, but the risk of permanent neurological injury is unknown and largely must be extrapolated from adult literature. In this article we present a series of 4 cases of longterm or permanent neurologic complications associated with epidural analgesia. Possible mechanisms of injury and implications for practice are discussed.

infants or to compare the safety of this wide range of drugs and preparations. Preclinical assessment of potential for spinal toxicity in validated models should be conducted before clinical delivery into the neuraxial space of neonates and children. Specific data that compare the efficacy and relative safety of available and potential new spinal analgesics are necessary for making a truly informed choice. The specific assessment of the potential toxicity of the drug must be the first priority.In the preclinical models of neuraxial analgesia, pharmacodynamic responses must be considered. For neonatal neuraxial delivery models, the intrathecal and epidural delivery techniques have been investigated in mice. The distribution of the injectate must be defined in any animal preclinical model. The volume must be adequate to deliver the drug to the correct dermatomes that evoke pain but insufficient to produce supraspinal redistribution. One assessment of correct placement is the observation of an appropriate behavioral response after injection. Evaluation of the safety or toxicity of spinal drugs can be made using the therapeutic ratio, that is, the dose that produces toxicity or the maximum tolerated dose versus the dose required to have a therapeutic effect. Studies that use developmental models that assess analgesic efficacy based on age-and dose-dependent antinociceptive analgesic effects can be performed. Adverse effects such as sedation, motor impairment, and cardiovascular changes can limit dose escalation and can be evaluated in preclinical laboratory studies to determine the therapeutic window at different ages. These adverse events are related to the physiologic and reversible pharmacodynamic profile of the drug. Other drugs at some concentrations or doses may have a direct effect on cellular function and cause irreversible changes in viability and represent tissue toxicity. Developmental toxicity is affected by postnatal age, activity-dependent neural development during postnatal life, and the developing spinal cord structure and function. These variables must also be considered and investigated in any preclinical assessment of developmental toxicity of neuraxially delivered drugs.The standards for preclinical evaluation of efficacy and toxicity of spinal analgesics must be based on several key characteristics that can mirror those of the human condition. These include a validated model and drug delivery that implies that the drug delivery occurs within the intrathecal space and that the injection protocol leads to an adequate and reliable distribution of the drug. The animal age must be such that the sequence of development of sensory and reflex systems can be correlated with stages in human infants. The other aspects of evaluations and outcomes must include blinded assessment, adequate histopathology investigations and analyses, age at the time of drug exposure, survival time after exposure, drug exposure and dose that must occur at neuraxial doses equaling or exceeding those destined for use in humans, an...

Mastocytosis is an orphan disease rarely encountered by practicing anesthesiologists. Children with mastocytosis often present for procedures or surgery requiring anesthesia. Because many of the medications commonly used in pediatric anesthesia have been reported to initiate mast cell activation, parents are often very anxious about their child's perioperative experience. Laboratory investigations of serum histamine assays associated with different anesthetic drugs have not been shown to predict mast cell degranulation in these patients. However, the pediatric literature suggests that children with disease limited to the skin rarely suffer serious side effects from anesthesia, and there are no reported fatalities. Preoperative prophylaxis is usually based on expert opinion and case reports. Detailed tables summarizing reports of anesthetic medications used for children with mastocytosis undergoing anesthesia, reported side effects, and suggested prophylaxis regimens are included in this review.

Patient blood management (PBM) strategies are needed in the neonate and paediatric population, given that haemoglobin thresholds used are often higher than recommended by evidence, with exposure of children to potential complications without meaningful benefit. A literature review was performed on the following topics: evidence-based transfusions of blood components and pharmaceutical agents. Other topics reviewed included perioperative coagulation assessment and perioperative PBM. The Transfusion and Anaemia Expertise Initiative (TAXI) consortium published a consensus statement addressing haemoglobin (Hb) transfusion threshold in multiple subsets of patients. A multicentre trial (PlaNeT-2) reported a higher risk of bleeding and death or serious new bleeding among infants who received platelet transfusion at a higher (50 000/μl) compared to a lower (25 000/μl) threshold. Recent data support the use of a restrictive transfusion threshold of 25 000/μl for prophylactic platelet transfusions in preterm neonates. The TAXI-CAB consortium mentioned that in critically ill paediatric patients undergoing invasive procedures outside of the operating room, platelet transfusion might be considered when the platelet count is less than or equal to 20 000/μl and there is no benefit of platelet transfusion when the platelet count is more than 50 000/μl. There are limited controlled studies in paediatric and neonatal population regarding plasma transfusion. Blood conservation strategies to minimise allogenic blood exposure are essential to positive patient outcomes neonatal and paediatric transfusion practices have changed significantly in recent years since randomised controlled trials were published to guide practice. Additional studies are needed in order to provide practice change recommendations.

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