Pediatric drug regulation: International perspectives.

There was a time when the predominant approach to exposing children to new drugs was to protect children from research. This has evolved over the past several decades into protecting children through research. To encourage pediatric studies and approval of pediatric medicines, governments have provided financial incentives as well as obligations/requirements for pharmaceutical companies to carry out pediatric studies in certain circumstances. The unique considerations for children have been acknowledged by the various governments and drug regulatory agencies through international dialogue and cooperation among patient and patient care representatives, regulatory agencies, and academic, clinical and manufacturing stakeholders. We describe pediatric drug regulation in five of the largest international drug regulatory agencies and additionally discuss efforts at international cooperation and discussion in pediatric drug regulation.

Pro: early extubation in the operating room following cardiac surgery in adults.

There is growing evidence that the general current approach in many centers of continued mechanical ventilation following cardiac surgery has evolved through historical experience rather than having a strong physiological basis in current practice. There is evidence going back several decades supporting very early (in the operating room [OR]) extubation in pediatric cardiac anesthesia. The authors provide evidence from numerous sources showing that extubation in the OR or shortly after arrival in the ICU is safe and cost-effective and is not prevented by the type of cardiac surgery or the use of cardiopulmonary bypass. They query if the paradigm should not be reversed and very early extubation be the routine unless contraindicated. Like any anesthetic technique, appropriate patient selection is called for, but this technique is widely appropriate.

The anesthetic management of cardiovascular trauma.

PURPOSE OF REVIEW: Although little new has been specifically written in recent years regarding the anesthesia management of cardiovascular trauma, two specific areas have seen recent interest and progress, namely the endovascular management of blunt thoracic aortic trauma and commotio cordis, or sudden death following blunt precordial injury. RECENT FINDINGS: Endovascular repair of thoracic aortic injury has been shown in multiple studies to have short to medium-term mortality and morbidity advantages over repair via thoracotomy. However, long-term (many years) outcome and the expenses required for long-term follow-up of endovascular repairs remain unknown. The risk of commotio cordis during sports activities has become more known to the general population. Recent studies have indicated a very specific limited time during the upstroke of the T-wave to be the critical time for injury, but specific channel involvement is unclear. SUMMARY: Although transesophageal echocardiography diagnosis of aortic trauma is very sensitive and specific, in general, the lack of immediate availability at all times of skilled echocardiographers and the immediate availability of spiral computed tomography scanners in trauma centers limits the use of transesophageal echocardiography as a first-line diagnostic tool. Endovascular repair of traumatic aortic injury is becoming routine. Commotio cordis is being increasingly recognized as a cause of acute post-traumatic sudden death.

Special article: a proposal for training in pediatric cardiac anesthesia.

Despite a relatively universally applicable knowledge base and skill set, training and experience in pediatric cardiac anesthesia in currently organized basic anesthesia and Adult Cardiothoracic Anesthesia fellowship programs are very limited and not uniformly available. Experience during Pediatric Anesthesia fellowship training is uniformly available but of limited duration and varying intensity. We present a schema, developed by a working group of the Congenital Cardiac Anesthesia Society, for training in pediatric cardiac anesthesia that pediatric cardiac anesthesia educators internationally should consider as a template to be modified as necessary.

Nitrous oxide in pediatric anesthesia: friend or foe?

PURPOSE OF REVIEW: Nitrous oxide has been used in clinical practice for over 150 years, often for pediatric procedures. Not only are there problems when used in patients with a variety of inborn errors of metabolism, but effects of nitrous oxide on the developing human brain are unknown. RECENT FINDINGS: A recent adult human trial found that the use of nitrous oxide was associated with increased adverse outcome. Animal studies in several species have shown that nitrous oxide can be associated with apoptosis in the developing brain. Nitrous oxide can also inhibit major enzymatic pathways and repeated exposure may lead to neurologic damage. Single nucleotide polymorphisms in at least one of these enzymes are common in the population. SUMMARY: There is a growing body of evidence that supports avoidance of nitrous oxide in both pediatric and adult patients, but the thousands of patients who have been exposed to nitrous oxide without apparent complications would suggest that further studies on long-term side effects and possible neurologic consequences need to be done.

Paediatric cardiac assistance in developing and transitional countries: the impact of a fourteen year effort.

BACKGROUND: Paediatric cardiac services are poorly developed or totally absent in underdeveloped countries. Institutions, foundations and interested individuals in those nations in which sophisticated paediatric cardiac surgery is practised have the ability to alleviate this problem by sponsoring paediatric cardio-surgical missions to provide care, and train local caregivers in developing, transitional, and third world countries. The ultimate benefit of such a programme is to improve the surgical abilities of the host institution. The purpose of this report is to present the impact of our programme over a period of 14 years. METHODS: We specifically reviewed our database of patients from our missions, our team lists, surgical results, and the number and type of personnel trained in the institutions that we have assisted. In order for the institution to be entered into the study, the foundation had to provide at least 2 months of training. In addition, the institution had to respond to a simple questionnaire concerning the number and types of surgery performed at their facility before and after intervention by the foundation. RESULTS: We made 140 trips to 27 institutions in 19 countries, with 12 of the visited institutions qualifying for inclusion. Of these, 9 institutions reported an increase in the number and complexity of cases currently being performed in their facility since the team intervened. This goal had not been accomplished in 3 institutions. The reasons for failure included the economic situation of the country, hospital and national politics, personality conflicts, and continued lack of hardware and disposables. CONCLUSIONS: Paediatric cardiac service assistance can improve local services. A significant commitment is required by all parties involved.

When nitrous oxide is no laughing matter: nitrous oxide and pediatric anesthesia.

Although often felt to be relatively innocuous, nitrous oxide can have significant metabolic effects in settings of abnormal vitamin B12 and B12-related metabolism in children. These conditions can be genetic or environmental. Symptoms may not appear until days to weeks after exposure to nitrous oxide. Although overt genetic diseases are relatively uncommon, the implications of nitrous oxide interactions with much more frequent but less symptomatically obvious single nucleotide polymorphisms are potentially more concerning. In addition, nitrous oxide can have direct and differing neurotoxic effects on both immature and aged brain, the clinical impact of which remains undetermined.

Pediatric cardiac surgery: an historical appreciation.

Many of the early, classic pediatric cardiac surgical operations were named after their originators. Some of these continue to be performed in the original form, many in modified form and some are obsolete. The development of many of these important early operations is reviewed and they are placed in the context of their times.