Maria Giuseppina Annetta

Ketamine: New Indications for an Old Drug

Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor for glutamate, though its effects are mediated by interaction with many others receptors. It has been introduced in clinical use since 1960s but today it is not largely employed as a general anaesthetic for its undesired psychic effects (emergence reactions) occurring in approximately 12% of patients. In the last decade, there has been a renewed interest in the use of subanaesthetic doses of ketamine for the treatment of acute and chronic pain. In the late 1990s, multiple prospective, randomised, controlled study has shown the efficacy of low dose of ketamine for postoperative pain relief, for analgesia during regional or local anaesthesia, and for opioid-sparing effect. At present, non-definitive conclusion can be drawn. More data are needed to define the possible long term effects and the clinical goal of ketamine use.

Sevoflurane improves the neuroendocrine stress response during laparoscopic pelvic surgery

PurposeStress response to surgery is modulated by several factors, including magnitude of the injury type of procedure (e.g., laparoscopy vs laparotomy) and type of anesthesia. Our purpose was to compare intra- and postoperative hormonal changes during isoflurane vs sevoflurane anesthesia, in a clinical model of well defined operative stress (laparoscopic pelvic surgery).MethodIn this prospective randomized clinical study, 20 women requiring laparoscopic pelvic surgery for benign ovarian cysts received either a standard isoflurane plus fentanyl (Group A) or sevoflurane plus fentanyl anesthesia (Group B). Blood samples were collected preoperatively 30 min after the beginning of surgery, at the end of surgery after extubation, and “two and four hours after the end of surgery. Intra- and postoperative plasma levels of norepinephrine, epinephrine, adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH) and prolactin (PRL) were measured.ResultsCatecholamine levels and postoperative pain were similar in both groups. Nonetheless, in comparison to Group A, Group B showed a significant decrease of ACTH, cortisol and GH levels (A vs B at the end of surgery: ACTH 160 ± 45 vs 100 ± 40 pg·mL−1; cortisol 45 ± 8 vs 23 ± 7 μg·dL−1; GH 3 ± 2 vs 0.8 ± 0.4 ng·mL−1; P < 0.001 for all), but enhanced PRL levels (A vs B, at 30 min after the beginning of surgery: 139 ± 54 vs 185 ± 22 ng·mL−1; at the end of surgery: 100±27 vs 141 ± 45 ng·mL−1; P < 0.001 for both).ConclusionsIn the clinical setting of low stress laparoscopic surgery, the type of volatile anesthetic significantly affected the stress response; the changes associated with sevoflurane suggested a more favourable metabolic and immune response compared to isoflurane.RésuméObjectifLa réaction au stress chirurgical dépend, entre autres, de l’importance du traumatisme chirurgical, du type d’intervention (laparoscopie vs laparotomie) et d’anesthésie. Nous voulions comparer les changements hormonaux pendant et après l’opération sous anesthésie à l’isoflurane, ou au sévoflurane, selon un modèle clinique bien défini de stress opératoire (intervention chirurgicale par laparoscopie pelvienne).MéthodeL’étude clinique, prospective et randomisée, a été faite auprès de 20 femmes devant subir une intervention par laparoscopie pelvienne pour des kystes bénins de l’ovaire. Les patientes ont reçu, soit une anesthésie normale à l’isoflurane avec du fentanyl (groupe A), soit au sévoflurane avec du fentanyl (groupe B). Le sang a été prélevé avant l’opération, 30 min après le début, à la fin après l’extubation et, deux et quatre heures après l’opération. Les niveaux plasmatiques peropératoire et postopératoire de noradrénaline, d’adrénaline, d’hormone adrénocorticotrope (ACTH), de cortisol, d’hormone de croissance GH) et de prolactine (PRL) ont été mesurés.RésultatsLes niveaux de catécholamine et la douleur postopératoire ont été similaires dans les deux groupes. Néanmoins, comparé au groupe A, le groupe B a affiché une baisse significative d’ACTH, de cortisol et de GH (A vs B à la fin de l’opération: ACTH 160 ± 45 vs 100 ±40 pg·mL−1; cortisol 45 ±8 vs 23 ±7 μg·dL−1; GH 3 ± 2 vs 0,8 ± 0,4 ng·mL−1; P < 0,001 pour toutes), et une hausse de PRL (A vs B, 30 min après le début de l’opération: 139 ± 54 vs 185 ± 22 ng·mL−1; à la fin de l’opération: 100 ± 27 vs 141 ± 45 ng·m−1; P < 0,001 pour les deux).ConclusionDans le cadre clinique d’une intervention laparoscopique de faible stress, le type d’anesthésique volatil utilisé a un effet significatif sur la réaction de stress; les changements associés au sévoflurane montrent une réaction immunitaire et métabolique plus favorable qu’avec l’isoflurane.

Treating nonthyroidal illness syndrome in the critically ill patient: still a matter of controversy.

The nonthyroidal illness syndrome (NTIS) is a clinical condition of abnormal thyroid function tests observed in patients with acute or chronic systemic illnesses. The laboratory parameters of NTIS usually include low serum levels of triiodothyronine, with normal or low levels of thyroxine and normal or low levels of thyroid-stimulating hormone. It is still a matter of controversy whether the NTIS represents a protective adaptation of the organism to a stressful event or a maladaptive response to illness that needs correction. Multiple studies have investigated the effect of thyroid hormone replacement therapy in certain clinical situations, such as caloric restriction, cardiac disease, acute renal failure, brain-dead potential donors, and burn patients. Treating patients with NTIS seems not to be harmful, but there is no persuasive evidence that it is beneficial. The administration of hypothalamic releasing factors in patients with NTIS appears to be safe and effective in improving metabolism and restoring the anterior pituitary pulsatile secretion in the chronic phase of critical illness. However, also this promising strategy needs to be explored further. Anyhow, an extremely prudent approach is needed if treatment is given. Much of the data appearing in the literature on the treatment of NTIS encourage further randomized controlled trials on large number of patients. At present, however, we believe that there is no indication for treating thyroid hormone abnormalities in critically ill patients until convincing proof of efficacy and safety is provided.

Use of Corticosteroids in Critically Ill Septic Patients: A Review of Mechanisms of Adrenal Insufficiency in Sepsis and Treatment

Adrenal insufficiency has being reported with increased frequency in critical ill patients with sepsis and other inflammatory states. Its incidence varies widely depending on the criteria used to define it and the patient population studied. Increased glucocorticoid action is essential in the stress response to acute injury and even minor degrees of adrenal insufficiency can be fatal. Recently the so-called relative or functional adrenal insufficiency (CIRCI) has been described: in this syndrome cortisol levels may be low or high but nonetheless inadequate to meet the elevated metabolic demand. Since laboratory diagnosis of adrenal insufficiency is still controversial, the diagnosis of ICU associated adrenal insufficiency is essentially a clinical diagnosis. Whether exogenous corticosteroid support may be beneficial in critical illness is still matter of debate: most international guidelines recommend that the decision to treat patients with corticosteroids should be based on clinical criteria (low blood pressure poorly responsive to vasopressor despite adequate fluid resuscitation) rather than on tests of the hypothalamic-pituitary-adrenal axis alone. As regards specifically the role of steroids in the treatment of sepsis and septic shock, at present there are no strong evidence-based recommendations. More studies are needed to reach consensus about several issues: which is the best target population, whether a cosyntropin test should be used to guide treatment, whether fludrocortisones should be given along with hydrocortisone, and how long treatment should continue.

Fat embolism syndrome

A 19-year-old man was admitted to our emergency department after a road accident. He presented with bilateral femoral fractures that were promptly treated with external fixators. After surgery, he was monitored in ICU. Twenty-four hours after admission, fever, tachycardia, dyspnea, and hypoxia appeared. He also became drowsy but arousable, confused, and agitated. Tracheal intubation was performed. A few hours later, reddishbrown nonpalpable axillary (Fig. 1a) and subconjunctival petechiae (Fig. 1b) appeared. Brain CT and chest X-ray were normal. Suspecting a fat embolism syndrome, we performed an MRI that showed multiple hyperintense puntiform lesions disseminated in deep white substance, basal ganglia, and thalamus on FLAIR imaging (Fig. 1c)

A new and promising tool to evaluate mass and structural changes of skeletal muscle in trauma patients

Loss of mass and function of skeletal muscle during critical illness is associated with poor clinical outcome, reduced ventilator-free days, increased length of ICU stay, increased mortality, high costs of health care, and delay of rehabilitation [1]. The magnitude of muscle impairment correlates with the severity of the illness, the entity of the inflammation, and the appropriateness of nutritional support [2, 3]. Recent papers have advocated the use of ultrasound evaluation of skeletal muscle [2, 4, 5] to get information about its thickness and structural changes, which can be related to the degree of myopathy and to the final functional outcome [5]. We are investigating the morphological changes of skeletal muscle in trauma patients during their stay in our ICU, by ultrasound evaluation of the rectus femuris (RF) and anterior tibialis (AT) muscles (transverse scan 15 cm above the patella and 5 cm below the fibular head, respectively), on day 0 (within 24 h after admission to ICU) and on day 21. We adopted a 5–7 MHz linear transducer and a well-defined setting for all patients (overall gain 67 %; time gain compensation in neutral position; focal zone set in the middle of the muscle). Muscle echogenicity is rated according to Heckmatt’s scale [6], which is a semiquantitative, four-rank score, the higher rank (D) corresponding to reduced visualization of bone surface and thus to a more severe degree of muscle fibrosis. In this preliminary study, we evaluated six severe trauma patients: three women/three men; age range 44–61 years; body mass index ranging from 23.1 to 28.2; injury severity score 29–52; all but one had brain injury, with Glasgow Coma Scale at admission ranging from 3 to 11; ICU stay was 25–52 days and survival was 100 %. In all patients, we found a progressive decrease in the muscle mass and a progressive increase of echogenicity, suggesting not only protein depletion but degenerative changes: during the ICU stay, the