Pharmacotherapy optimization for rapid sequence intubation in the emergency department.

PURPOSE: Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. SUMMARY: There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. AREAS FOR FUTURE RESEARCH: The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.

New prospects for drug treatment in Cushing disease.

Hypercortisolism induced by Cushing disease causes high morbidity and mortality. The treatment of choice is pituitary surgery, but it often fails to achieve cure, and other treatment modalities (radiotherapy, bilateral adrenalectomy) may therefore be required. If these treatments are not effective or while waiting for their results, hypercortisolism should be controlled with drugs. The classical drug treatments are those that act by inhibiting cortisol secretion by the adrenal gland (ketoconazole, metyrapone, mitotane, etomidate). The preliminary results of a new drug (LCI699) which is a potent enzyme inhibitor of cortisol secretion have been reported. A clinical trial of the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, has just been published. The drugs deserving more attention today are those with a direct action on the tumor by inhibiting ACTH secretion: somatostatin analogues (pasireotide), dopamine agonists (cabergoline), PPAR-γ, and retinoic acid. A special review is made of the available clinical trials with pasireotide and cabergoline.

Median effective effect-site concentration of intravenous anesthetics for loss of consciousness in neoadjuvant chemotherapy patients.

BACKGROUND: In recent years, increasing numbers of patients are accepting neoadjuvant chemotherapy before their operation in order to get a better prognosis. But chemotherapy has many side-effects. We have observed that patients who accepted neoadjuvant chemotherapy are more sensitive to anesthetics. The aim of this study was to determine the median effective dose (EC(50)) of intravenous anesthetics for neoadjuvant chemotherapy patients to lose consciousness during target-controlled infusion. METHODS: Two hundred and forty breast cancer patients undergoing elective operations were assigned to six groups according to treatment received before their operation and the use of intravenous anesthetics during anesthesia; non-adjuvant chemotherapy + propofol group (group NP, n = 40), Taxol + propofol group (group TP, n = 40), adriamycin + cyclophosphamide + 5-Fu + propofol group (group CP, n = 40), non-adjuvant chemotherapy + etomidate group (group NE, n = 40), taxol + etomidate group (group TE, n = 40), adriamycin + cyclophosphamide + 5-Fu + etomidate group (group CE, n = 40). We set the beginning effect-site concentration (Ce) of propofol as 3.0 µg/ml and etomidate as 0.2 µg/ml. The concentration was increased by steps until the patient was asleep, (OAAS class I-II), then gave fentanyl 3 µg/kg and rocuronium 0.6 mg/kg and intubated three minutes later. The patients' age, height, and weight were recorded. BIS was recorded before induction, at the initial effect-site concentration and at loss of consciousness. The effect-site concentration was recorded when patient lost consciousness. RESULTS: There were no significant differences between groups in general conditions before treatment; such as BIS of consciousness, age, sex and body mass index. The EC(50) of propofol in the NP, TP and CP groups was 4.11 µg/ml (95%CI: 3.96 - 4.26), 2.94 µg/ml (95%CI: 3.36 - 3.47) and 2.91 µg/ml (95%CI: 3.35 - 3.86), respectively. The EC50 of etomidate in the NE, TE and CE groups was 0.61 µg/ml (95%CI: 0.55 - 0.67), 0.38 µg/ml (95%CI: 0.33 - 0.44), and 0.35 µg/ml (95%CI: 0.34 - 0.36), respectively. There was no significant difference of BIS level before induction or in BIS50 level in any group when patients lost consciousness. CONCLUSIONS: The EC(50) of intravenous anesthetics to cause loss of consciousness in neoadjuvant chemotherapy groups is lower than in the control group. There was no significant difference of BIS level at which patients lost consciousness.

Ischemia-reperfusion injury in skeletal muscle: comparison of the effects of subanesthetic doses of ketamine, propofol, and etomidate.

BACKGROUND: Interest in the effects of anesthetics in skeletal ischemia-reperfusion injury (IRI) has recently emerged. Thus, the objective was to compare the effects of subanesthetic doses of ketamine, propofol, and etomidate in a skeletal IRI model. METHODS: IRI was applied to rats by tourniquet method. Under thiopental anesthesia, five experimental groups were established as follows: (1) sham-control, (2) IRI, (3) IRI+Ketamine, (4) IRI+Propofol, and (5) IRI+Etomidate. Malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were measured in skeletal muscle via a spectrophotometer. Zinc, iron, copper, and selenium were evaluated by atomic absorption spectrophotometer. RESULTS: While the values of malondialdehyde and glutathione peroxidase were higher and lower, respectively, those of superoxide dismutase and catalase were identical in IRI group in comparison with sham-control. Zinc displayed a decrease in IRI group; however, no differences in iron and copper levels were determined. In rats treated with subanesthetic doses of ketamine, elevated malondialdehyde levels in IRI group were reversed to control levels by each dose. While each dose of ketamine decreased superoxide dismutase activities in comparison with IRI group, a reduction in catalase activity was only seen in 3mg/kg ketamine-treated rats. The attenuated glutathione peroxidase activity seen in IRI was greatly reversed by ketamine administration in all doses. No differences in zinc, copper, and iron levels were detected between IRI and ketamine-treated groups. Similar results were obtained either by the administration of propofol or etomidate. CONCLUSIONS: Subanesthetic doses of ketamine, propofol and etomidate displayed beneficial effects in IRI.

Therapeutic coma or neuroprotection by anaesthetics.

Some surgical patients are at an increased risk for developing cerebral ischaemia. A subset of these patients is believed to benefit from putative cerebroprotective effects of anaesthetic agents. Therefore, in this setting these drugs could have therapeutic modalities, besides their auxiliary functions to make surgery possible. However, both animal and especially human data are very disappointing. Only the barbiturates and isoflurane have an experimental record warranting further research to delineate proper indications for their use as neuroprotective agents in surgical patients.