Interactions of the protease inhibitor, ritonavir, with common anesthesia drugs.

The protease inhibitor, ritonavir, is a strong inhibitor of CYP 3A. The drug is used for management of the human immunovirus and is currently part of an oral antiviral drug combination (nirmatrelvir-ritonavir) for the early treatment of SARS-2 COVID-19-positive patients aged 12 years and over who have recognized comorbidities. The CYP 3A enzyme system is responsible for clearance of numerous drugs used in anesthesia (e.g., alfentanil, fentanyl, methadone, rocuronium, bupivacaine, midazolam, ketamine). Ritonavir will have an impact on drug clearances that are dependent on ritonavir concentration, anesthesia drug intrinsic hepatic clearance, metabolic pathways, concentration-response relationship, and route of administration. Drugs with a steep concentration-response relationship (ketamine, midazolam, rocuronium) are mostly affected because small changes in concentration have major changes in effect response. An increase in midazolam concentration is observed after oral administration because CYP 3A in the gastrointestinal wall is inhibited, causing a large increase in relative bioavailability. Fentanyl infusion may be associated with a modest increase in plasma concentration and effect, but the large between subject variability of pharmacokinetic and pharmacodynamic concentration changes suggests it will have little impact on an individual patient, especially when used with adverse effect monitoring. It has been proposed that drugs that have no or only a small metabolic pathway involving the CYP 3A enzyme be used during anesthesia, for example, propofol, atracurium, remifentanil, and the volatile agents. That anesthesia approach denies children of drugs with considerable value. It is better that the inhibitory changes in clearance of these drugs are understood so that rational drug choices can be made to tailor drug use to the individual patient. Altered drug dose, anticipation of duration of effect, timing of administration, use of reversal agents and perioperative monitoring would better behoove children undergoing anesthesia.

Anaesthesia and airway management in mucopolysaccharidosis.

This paper provides a detailed overview and discussion of anaesthesia in patients with mucopolysaccharidosis (MPS), the evaluation of risk factors in these patients and their anaesthetic management, including emergency airway issues. MPS represents a group of rare lysosomal storage disorders associated with an array of clinical manifestations. The high prevalence of airway obstruction and restrictive pulmonary disease in combination with cardiovascular manifestations poses a high anaesthetic risk to these patients. Typical anaesthetic problems include airway obstruction after induction or extubation, intubation difficulties or failure [can't intubate, can't ventilate (CICV)], possible emergency tracheostomy and cardiovascular and cervical spine issues. Because of the high anaesthetic risk, the benefits of a procedure in patients with MPS should always be balanced against the associated risks. Therefore, careful evaluation of anaesthetic risk factors should be made before the procedure, involving evaluation of airways and cardiorespiratory and cervical spine problems. In addition, information on the specific type of MPS, prior history of anaesthesia, presence of cervical instability and range of motion of the temporomandibular joint are important and may be pivotal to prevent complications during anaesthesia. Knowledge of these risk factors allows the anaesthetist to anticipate potential problems that may arise during or after the procedure. Anaesthesia in MPS patients should be preferably done by an experienced (paediatric) anaesthetist, supported by a multidisciplinary team (ear, nose, throat surgeon and intensive care team), with access to all necessary equipment and support.

An audit of the use of an opiate sparing, multimodal analgesic regime in children with Sleep Disordered Breathing/Obstructive Sleep Apnoea undergoing adenotonsillectomy.

OBJECTIVES: Children with Sleep Disordered Breathing/Obstructive Sleep Apnoea have an increased incidence of respiratory complications following adenotonsillectomy. This may be partly related to an increase in sensitivity to opiates. An audit of such cases undergoing adenotonsillectomy was performed with the following aims: METHODS: All patients had Sleep Disordered Breathing/Obstructive Sleep Apnoea confirmed preoperatively by Overnight Oximetry Studies. Oximetry data was expressed as the lowest recorded saturation (SpO2 Low %) and number of significant desaturations (see text) per hour (ODI4%). Case notes and oximetry studies were scrutinized for relevant perioperative anaesthetic and analgesic data, risk factors and complications. RESULTS: The overall incidence of major and minor respiratory complications was low (1.6% and 27% respectively). Children who suffered any complication were more likely to be younger (p=0.0078), have a lower SpO2 Low (p=0.004) and higher ODI4% (p=<0.0001). Multiple logistic regression showed ODI4% to be the best predictor of a potential respiratory complication (p=0.0032). An ODI4% of >8 may be the best cut off point in predicting complications (AUC=0.78, sensitivity=0.90) but it showed a poor specificity (0.57). Primary/secondary haemorrhage occurred in 0.4%/1.2% respectively and postoperative nausea and vomiting in 4.4%. CONCLUSIONS: A low dose opiate-based, multi modal analgesic regime appears to be effective and safe in children with Sleep Disordered Breathing/Obstructive Sleep Apnoea undergoing adenotonsillectomy.

Use of the Esophageal Doppler Machine to help guide the intraoperative management of two children with pheochromocytoma.

The anesthetic management of pheochromocytoma has been based upon the intraoperative control of blood pressure and fluid balance following adequate preoperative preparation. This can be difficult, especially in the presence of significant comorbidity such as cardiac or renal dysfunction. Two cases of children with pheochromocytoma are reported where the introperative management of fluid balance and blood pressure control were guided by measurement of changes in descending aortic blood flow using an esophageal Doppler probe. The advantages of such a technique compared with more invasive monitors are discussed.

An unknown second tracheoesophageal fistula: a rare cause of postoperative respiratory failure.

The case of a 6-year-old boy who developed complications following gastric interposition surgery for severe, recurrent esophageal stricture is reported. Investigation of his pleural effusion revealed a rare and unexpected complication.