Molecular Bases for Anesthetic Agents: Halothane as a Halogen- and Hydrogen-Bond Donor.

Although instrumental for optimizing their pharmacological activity, a molecular understanding of the preferential interactions given by volatile anesthetics is quite poor. This paper confirms the ability of halothane to work as a hydrogen-bond (HB) donor and gives the first experimental proof that halothane also works as a halogen-bond (HaB) donor in the solid state and in solution. A halothane/hexamethylphosphortriamide co-crystal is described and its single-crystal X-ray structure shows short HaBs between bromine, or chlorine, and the phosphoryl oxygen. New UV/Vis absorption bands appear upon addition of diazabicyclooctane and tetra(n-butyl)ammonium iodide to halothane solutions, indicating that nitrogen atoms and anions may mediate the HaB-driven binding processes involving halothane as well. The ability of halothane to work as a bidentate/tridentate tecton by acting as a HaB and HB donor gives an atomic rationale for the eudismic ratio shown by this agent.

Analgo-sedation of patients with burns outside the operating room.

Following the initial resuscitation of burn patients, the pain experienced may be divided into a 'background' pain and a 'breakthrough' pain associated with painful procedures. While background pain may be treated with intravenous opioids via continuous infusion or patient-controlled analgesia (PCA) and/or less potent oral opioids, breakthrough pain may be treated with a variety of interventions. The aim is to reduce patient anxiety, improve analgesia and ensure immobilization when required. Untreated pain and improper sedation may result in psychological distress such as post-traumatic stress disorder, major depression or delirium. This review summarizes recent developments and current techniques in sedation and analgesia in non-intubated adult burn patients during painful procedures performed outside the operating room (e.g. staple removal, wound-dressing, bathing). Current techniques of sedation and analgesia include different approaches, from a slight increase in background pain therapy (e.g. morphine PCA) to PCA with rapid-onset opioids, to multimodal drug combinations, nitrous oxide, regional blocks, or non-pharmacological approaches such as hypnosis and virtual reality. The most reliable way to administer drugs is intravenously. Fast-acting opioids can be combined with ketamine, propofol or benzodiazepines. Adjuvant drugs such as clonidine or NSAIDs and paracetamol (acetaminophen) have also been used. Patients receiving ketamine will usually maintain spontaneous breathing. This is an important feature in patients who are continuously turned during wound dressing procedures and where analgo-sedation is often performed by practitioners who are not specialists in anaesthesiology. Drugs are given in small boluses or by patient-controlled sedation, which is titrated to effect, according to sedation and pain scales. Patient-controlled infusion with propofol has also been used. However, we must bear in mind that burn patients often show an altered pharmacokinetic and pharmacodynamic response to drugs as a result of altered haemodynamics, protein binding and/or increased extracellular fluid volume, and possible changes in glomerular filtration. Because sedation and analgesia can range from minimal sedation (anxiolysis) to general anaesthesia, sedative and analgesic agents should always be administered by designated trained practitioners and not by the person performing the procedure. At least one individual who is capable of establishing a patent airway and positive pressure ventilation, as well as someone who can call for additional assistance, should always be present whenever analgo-sedation is administered. Oxygen should be routinely delivered during sedation. Blood pressure and continuous ECG monitoring should be carried out whenever possible, even if a patient is undergoing bathing or other procedures that may limit monitoring of vital pulse-oximetry parameters.