The power of unbiased genetic screens to discover novel anesthetic targets.

To the Editor: We are writing in response to Dr. Forman’s1 editorial “The Expanding Genetic Toolkit for Exploring Mechanisms of General Anesthesia” in the April issue of ANESTHESIOLOGY. Dr. Forman covers many excellent points about the use of genetics in understanding anesthetic mechanisms. However, we think that he has overlooked, and perhaps unintentionally discounted, the key ability of an unbiased forward genetic screen to study anesthetic action. A forward screen generates mutations randomly and then looks for those mutations that affect a particular trait. Its unique beauty or power is that it can discover novel mechanisms that would not be found if one presupposed to know an anesthetic target. Forward genetic screens have identified plausible possible targets of volatile anesthetics. They have included leak channels,2 neurotransmitter release machinery,3 and mitochondria.4 All three possibilities have been occurs frequently after the acute phase of trauma-induced coagulopathy.14,15 Dr. Flores suggests the use of multilevel continuous intercostal nerve block catheter in a patient with flail chest. Although the risk of epidural hematoma may be lower with intercostal nerve blocks compared with epidural analgesia, other risks such as pneumothorax/hematothorax and inadequate efficacy may limit its use under the condition described in our case scenario. We need to develop specific outcome-oriented clinical pathways in critical care medicine that do not exclusively take into account the data taken from elective surgical procedures in the operating room. In patients with flail chest presenting with traditional contraindications for neuraxial analgesia, careful risk–benefit analysis may indicate that epidural analgesia improves important outcome measures. We believe that thromboelastography or thromboelastometry and aggregometry (if available) are helpful instruments for decision support in such a case scenario.