Inflammatory response to cardiopulmonary bypass with enoximone or steroids in patients undergoing myocardial revascularization: a preliminary report study.

OBJECTIVE: Recent reports have showed an antiinflammatory effect of phosphodiesterase III inhibitors (PDEi) in patients undergoing cardiopulmonary bypass (CPB). We sought to evaluate the immunological and hemodynamic response to enoximone and methylprednisolone in patients undergoing CABG. DESIGN: Prospective, randomized, controlled study. SETTING: Cardiac surgery unit in a university hospital. PATIENTS: 40 patients undergoing CPB-CABG. INTERVENTIONS: Patients receive enoximone (20, Group A) or methylprednisolone (20, Group B). MEASUREMENTS AND MAIN RESULTS: Hemodynamic response was evaluated by Swan-Ganz catheter serial measurements and perioperative Lactate and Troponin I leakage, immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpah, IFN-gamma, IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of surgery (T2), ITU admission (T3), 24 hs (T4) postoperatively. Morbidity and mortality were comparable between the two groups. Group A demonstrated higher cardiac index at T2 (2.93 l/min m2 vs 2.06, p < 0.001), at T3 (3.01 vs 2.18, p < 0.001), lower indexed systemic vascular resistance at T2 (2,044 dyne s cm-5 m-2 vs 3,132, p < 0.001). Except for higher TNF-alpha in Group B at T2 (15.89 vs 22.68, p = 0.005) proinflammatory cytokines were comparable. IL-10 was higher in Group B at any postoperative time (IL-10: T1 80.74 vs 143.3, p < 0.001, T2 165.7 vs 377.4, p < 0.001, T3 203.4 vs 443.5, p < 0,001, T4 251.8 vs 437.1, p < 0.001), whereas IL-4 and IFN-gamma proved higher in Group A at all time-points (IL-4: T1 45.9 vs 31.2, p = 0.008, T2 67.2 vs 39.7, p < 0.001, T3 77.9 vs 39.2, p < 0.001, T4 102.9 vs 42.2, p < 0.001. IFN-gamma: T1 25.8 vs 15.8, p < 0.001, T2 52.2 vs 30.3, p < 0.001, T3 78.4 vs 40.8, p < 0.001, T4 159.9 vs 67.4, p < 0.001). CONCLUSIONS: Despite comparable major clinical endpoints enoximone showed a different antiinflammatory pattern compared to methylprednisolone, however, the better hemodynamic response in enoximone compared to methylprednisolone suggests enoximone as a potential antiinflammatory tool to improve the outcome in cardiac surgery.

Inflammatory response after cardiopulmonary bypass: a randomized comparison between conventional hemofiltration and steroids.

AIM: Recent reports have shown anti-inflammatory effects with conventional hemofiltration (CUF) in patients undergoing cardiopulmonary bypass (CPB). The aim of this study was to evaluate the immunological and the hemodynamic response to CUF or metilprednisolone in patients undergoing coronary artery bypass grafting. METHODS: Twenty-four consecutive patients were prospectively randomized to receive CUF (12 patients, Group A) or metilprednisolone (12 patients, Group B). Hemodynamic response was evaluated by Swan-Ganz catheter, immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpha, IFN-gamma, IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of surgery (T2), ITU admission (T3) and 24 hours (T4). Troponin I was measured at the same time-points. Hematological and coagulative controls were performed. RESULTS: Morbidity and mortality were comparable between the two groups. Group A demonstrated lower cardiac index at T1 (2.1 +/- 0.69 L/min m2 vs. 3.917 +/- 1.28, P = 0.034) without significantly higher indexed-systemic-vascular-resistances at the end of surgery (1 101 +/- 434.3 dyne s cm(-5) m(-2) vs. 797.7 +/- 316.67, P = 0.233). When proinflammatory and anti-inflammatory cytokines were considered, all improved during the postoperative time course, without differences between the 2 Groups (P = NS). Hematological and coagulative data were similar in the two groups, in terms of white blood cells, platelets, prothrombin time, and activated partial thromboplastin time (P = NS). CONCLUSIONS: Anti-inflammatory action of CUF was comparable to steroids, thus determining a similar proinflammatory response to CPB. However, hemodynamics was slightly impaired by CUF. Therefore, there is no reason to prefer CUF to steroids in patients undergoing elective CABG.

Evidence for a differential interaction of buprenorphine with opiate receptor subtypes controlling prolactin secretion.

We studied the effects of various doses of the opiate derivative buprenorphine on serum prolactin levels and whether these effects could be counteracted by pretreatment with the opiate receptor blocker naloxone. The administration of increasing doses of buprenorphine exerted a dual effect on serum prolactin levels. At low doses (3, 10 and 30 micrograms/kg) this agent increased serum prolactin levels. This effect disappeared with increasing doses (100 and 300 micrograms/kg), and at the highest doses (1000 and 3000 micrograms/kg) the levels of serum prolactin decreased. Naloxone (30 mg/kg) decreased serum prolactin levels and reversed both the stimulatory and the inhibitory action of buprenorphine. These data are compatible with the hypothesis that buprenorphine could interfere with two different, but inter-dependent receptors: at low doses the oripavine derivative could act at one receptor site to cause an increase of serum prolactin, whereas at higher doses it could interact with a second site of lower affinity that is responsible for the inhibition of prolactin secretion. When buprenorphine (at high doses) activates the lower affinity site, the interaction with this receptor counteracts and reverses the effects of the high affinity site. On the basis of this hypothesis, naloxone should block both receptors.

Hemodynamic effects of levosimendan in patients with low-output heart failure after cardiac surgery.

Following cardiac surgery, low-output syndrome is relatively common. Since this condition can lead to serious consequences, this postsurgical, low-output state should be reversed whenever possible. Patients with low-output syndrome need drug and fluid management aimed at enhancing cardiac contractility and at facilitating optimal myocardial loading. The objective of this pilot study was to evaluate whether benefits of levosimendan, a new calcium-sensitizing agent approved for treatment of patients with acute exacerbation of chronic heart failure, could be extended to patients with low-output syndrome following cardiac surgery. For this study, each patient was given levosimendan as a loading dose of 12 microg/kg over 10 minutes, followed by a continuous infusion of 0.1 microg/kg/min for 12 hours. Of 11 postsurgical patients with severely impaired cardiac output and hemodynamic compromise, 8 patients (73%) showed evidence of combined hemodynamic improvement (> 30% increase in cardiac index and PCWP corrected to < 18 mmHg) within 3 h after the start of levosimendan infusion. Specifically, cardiac index and stroke volume were significantly increased, while mean arterial pressure, indexed systemic vascular resistance, mean pulmonary pressure, right arterial pressure, and pulmonary capillary wedge pressure were all significantly lowered. Taken together, such changes showed enhanced cardiac output along with significantly decreased preload and afterload--conditions associated with recovery of cardiac function. Levosimendan is thus highly favorable for short-term treatment of patients with low cardiac output following cardiac surgery.

Tracheal rupture secondary to orotracheal intubation.

A case of tracheal rupture due to orotracheal intubation performed for anaesthesiological procedures is described. It is very likely that this rare complication was favoured by some anatomical factors, which were responsible for a difficult intubation. Tracheal rupture was diagnosed by endoscopy and treated by a decompressive tracheostomy.

[Obesity and outcomes in the ICU: an observational study]. / Obesità ed outcome in UTI: uno studio osservazionale.

OBJECTIVES: We examined the relationships among Body Mass Index (BMI) with or without Metabolic Syndrome (MetS), ICU length of stay (ICU-LOS), duration of mechanical ventilation and mortality among ICU patients. MATERIALS AND METHODS: This prospective observational study included all patients hospitalized in a 10-bed polyvalent ICU over a period of one year and seven months. We divided the studied population into 4 groups by BMI values: group A: between 18.5 and 24.9 (n=369); group B1: 25-39.9 without MetS (n=86); B2 group: 25-39.9 with MetS (n=72); group C: >40 (n=42). Major exclusion criteria were: age <18 years, death or cerebral death within 24 hours from ICU admission. The chi square test and the variance analysis were used to compare groups. Variables significantly associated with ICU mortality were entered in a multiple regression model, allowing the determination of independent predictors. RESULTS: 620 patients were included in the study. Their SOFA score was between 8 and 15. Significant differences between B1 and B2 subgroups were observed in ICU-LOS (p <0.01), duration of mechanical ventilation (p <0.01) and ICU mortality (p <0.01). We found no statistically significant differences in mortality between B2 and C groups, as well as between A and B1 groups (42.34%/45.15% vs 16.27%/19.07%, respectively). We found that a BMI >25 with MetS was an independent predictive factor of: lower ICU-LOS, lower duration of mechanical ventilation, higher mortality rate. CONCLUSIONS: In our study, a BMI >25 with MetS was significantly associated with increased morbidity and mortality in ICU patients.

Intensive versus conventional insulinotherapy after elective and on-pump myocardial revascularization: a prospective and randomized study.

OBJECTIVES: Strict glycemic control is increasingly recognized as an important goal in a broad spectrum of critically ill patients. We analyzed the inflammatory and clinical response of patients submitted to intensive or conventional insulinotherapy in a specific clinical context. MATERIALS AND METHODS: We analyzed a prospective and randomized collected database of an Intensive Care Unit (ICU) in a University Hospital. The database comprised a total of 50 patients aged 30 to 80 (ASA II-III) who underwent elective and on-pump myocardial revascularization from September 2006 to June 2008. On ICU admission, patients were randomly assigned to Group 1 (intensive insulinotherapy) or Group 2 (conventional insulinotherapy). Data collected included glucose and lactate blood levels, haemodynamic parameters, cytokines (TNFalpha, IL-6, IL-8, IL-10), C-Reactive Protein, white blood cells and platelets blood levels, body temperature, Sequential Organ Failure Assessment (SOFA) score, Infection Probability Score (IPS) and ICU length of stay (LOS). Within-between group analysis, one-way ANOVA and unpaired t-test were used when appropriate. RESULTS: Pre- and perioperative variables were comparable between the two groups (p=NS for all measurements). Glucose and lactate blood levels were lower in Group 1 (p less than 0.0001). Stroke Volume Index was higher in Group 1 (p less than 0.05). Moreover, we observed statistically significant differences between groups in terms of inflammatory parameters and severity scores. No difference was observed in ICU LOS. CONCLUSIONS: Intensive insulinotherapy after elective on-pump myocardial revascularization significantly modulates the inflammatory response. Different inflammatory patterns could correlate with different clinical response as suggested by SOFA and IP score analysis.

Postoperative pain treatment SIAARTI Recommendations 2010. Short version.

The aim of these recommendations is the revision of data published in 2002 in the "SIAARTI Recommendations for acute postoperative pain treatment". In this version, the SIAARTI Study Group for acute and chronic pain decided to grade evidence based on the "modified Delphi" method with 5 levels of recommendation strength. Analgesia is a fundamental right of the patient. The appropriate management of postoperative pain (POP) is known to significantly reduce perioperative morbidity, including the incidence of postoperative complications, hospital stay and costs, especially in high-risk patients (ASA III-V), those undergoing major surgery and those hospitalized in a critical unit (Level A). Therefore, the treatment of POP represents a high-priority institutional objective, as well as an integral part of the treatment plan for "perioperative disease", which includes analgesia, early mobilization, early enteral nutrition and active physiokinesitherapy (Level A). In order to improve an ACUTE PAIN SERVICE organization, we recommend: --a plan for pain management that includes adequate preoperative evaluation, pain measurement, organization of existing resources, identification and training of involved personnel in order to assure multimodal analgesia, early mobilization, early enteral nutrition and active physiokinesitherapy (Level A); --the implementation of an Acute Pain Service, a multidisciplinary structure which includes an anesthetist (team coordinator), surgeons, nurses, physiotherapists and eventually other specialists; --referring to high-quality indicators in establishing an APS and considering the following key points in its organization (Level C): --service adoption; --identifying a referring anesthetist who is on call 24 hours a day; --patient care during the night and weekend; --sharing, drafting and updating written therapeutic protocols; --continuous medical education; --systematic pain assessment; --data collection regarding the efficacy and safety of the implemented protocols; --at least one audit per year. --a preoperative evaluation, including all the necessary information for the management of postoperative analgesia (Level C); --to adequately inform the patient about the risks and benefits of drugs and procedures used to obtain the maximum efficacy from the administered treatments (Level D). We describe pharmacological and loco-regional techniques with special attention to day surgery and difficult populations. Risk management pathways must be the reference for early identification and treatment of adverse events and chronic pain development.

Weaning from mechanical ventilation: an open issue.

Weaning from mechanical ventilation represents one of the main challenges facing ICU physicians. Difficult weaning affects about 25% of critical patients undergoing mechanical ventilation. Its duration correlates on one hand with pathophysiological aspects of the underlying disease and, on the other hand, with other factors such as the development of neuromyopathy of the critically ill patient, prolonged use of sedative-hypnotic drugs and, most of all, physicians' reluctance to identify the correct timing of therapeutic steps for weaning and subsequent extubation. The goal of adopting weaning protocols is to overcome problems due to an exclusively clinical opinion. Protocols have to be used together with daily clinical evaluation of the patient and the procedure must be carried out by an ICU team of both medical and nursing staff. Attempts to wean a patient from a ventilator and extubate him should be made through a spontaneous breathing trial (SBT) with T-tube or pressure support ventilation (PSV) with pressure support of 7-8 cmH(2)O +/- PEEP =/> 4 cmH(2)O. Proper recourse to non invasive mechanical ventilation (NIMV) and an accurate timing for tracheostomy are effective tools which can be used by physicians to facilitate weaning and to improve patient outcomes.

[Preemptive analgesia or balanced periemptive analgesia?]. / Preemptive analgesia o balanced periemptive analgesia?

"Preemptive analgesia" means that analgesia given before the painful stimulus prevents or reduces subsequent pain. The concept of preemptive analgesia originates from basic science and experimental studies. However, in some clinical studies preemptive effect is not always present. The authors think that it happens for: differences among experimental models and clinical reality, wrong use of some pharmacological knowledges, some methodological errors in clinical research. The authors analyze these factors and review in a critical manner clinical studies on preemptive analgesia. In some operations, only one administration of an analgesic drug, before surgery, is not sufficient to produce an evident preemptive effect. Postoperative pain can be reduced making a pharmacological treatment before surgery, for the whole time of painful stimulus. For this reason, the term "preemptive analgesia", like "analgesia given before surgery" is not adequate. The authors suggest that the concept of prevention of postoperative pain is well defined by the term of "balanced periemptive analgesia"; it is a new approach that use many modalities of analgesia in different times to prevent and control painful stimulus for the whole time of its origin: before and/or during operation and, if necessary, in the postoperative period for the residual pain.

[Preparation of a polyvalent antiserum specific for human muscle proteins. I. Muscle extraction: a macromethod and a micromethod]. / Preparazione di un antisiero polivalente specifico per le proteine muscolari umane. I. Preparazione dell'estratto muscolare: un macrometodo ed un micrometodo.

Protein metabolism may be upset dramatically by several pathological condition such as starvation, malnutrition, surgical stress. Serum proteins have been investigated in many works but very few studies exist about muscle and organ proteins. This article describes two methods for extraction of muscle water soluble proteins: a macromethod that uses some hundred grams of tissue, and a micromethod that starts from a little muscle biopsia. Extracts have been tested for protein content by electrophoresis on cellulose acetate and isoelectrofocusing on polyacrylamide gel and have shown a rich variety of protein fractions.

[Preparation of a polyvalent antiserum specific for human muscle proteins. II. Animal immunization and purification of the antiserum]. / Preparazione di un antisiero polivalente specifico per le proteine muscolari umane. II. Immunizzazione degli animali e purificazione dell'antisiero ottenuto.

A new preparation technique to raise rabbit antisera against human water-soluble muscle proteins is presented. Immunization, blood collection and further purification of antibody fraction in serum are described in detail. The present method is fast and easy to perform; chromatography and dialysis are not required and antisera so produced lend themselves to immunoelectrophoretic evaluation of human water-soluble muscle proteins.

Propofol infusion and auditory evoked potentials.

The effects of propofol on auditory evoked potentials (brainstem and middle latency responses) were recorded in six patients. Two different infusion rates were used, 54 and 108 micrograms/kg/minute. Effects on brainstem responses were not found. Regression of amplitude and latency of middle latency auditory potentials were dose related (p less than 0.01).

[Neuronal plasticity and neuropathic pain]. / Neuroplasticità e dolore neuropatico.

The authors have analysis the physiopathology of neuropathic pain, focusing in particular on the plastic phenomena at the level of the central nervous system. Plastic phenomena take the form of anatomic and neurochemical alterations. In relation to the former, excitatory amino acids play a fundamental role, causing a state of hypersensitivity of N-menthyl-D aspartate (NMDA) receptors (excitation toxicity) which in turn cause the degeneration of inhibitory interneurons localised in the I-III laminae of the dorsal cornu. This hyperactivation is responsible for the presence of a discharge input that lasts for minutes after a nociceptive stimulus, a phenomenon known as long-term potentiation (LTP) on long term depression (LTD). The authors also analysed the role of other neurotransmitters and their possible interactions. Neurochemical alterations are coupled with anatomic modifications, like sprouting, at the level of the dorsal cornu laminae and dorsal root ganglia. These neuroplastic phenomena lead to an alteration in the central mechanisms of pain, for A-fibre mediated mechano-allodynia, a clinical phenomenon that differs from thermal hyperalgesia in both physiopathology and clinical prognosis. The role played by the sympathetic system in neuropathic pain is also discussed. The authors also raise a number of clinical considerations regarding the different nature of spontaneous pain, allodynia and hyperalgesia. New physiopathological knowledge is a useful tool for pharmacological and clinical research, as well as for treatment of syndromes secondary to neuropathic pain.

Nitric oxide inhibits neutrophil adhesion during experimental extracorporeal circulation.

BACKGROUND: Myocardial and pulmonary injuries often occur after cardiopulmonary bypass, mediated in part by neutrophil activation and adhesion to endothelial cells. The effects of nitric oxide (NO) administration on neutrophil adhesion to endothelial cells after simulated extracorporeal circulation were investigated. METHODS: Two identical extracorporeal circulation circuits were primed with fresh human blood and circulated for 2 h at 37 degrees C. Nitric oxide at a 40-ppm concentration was added to one of the oxygenators in each pair. Neutrophil CD11b/CD18 expression and their adhesion to human umbilical vein endothelial cell monolayers were assayed in leukocytes isolated from samples drawn from the circuit 30, 60, 90, and 120 min after circulation began. In another series of experiments, blocking monoclonal antibodies to both neutrophil CD11b and CD18 were incubated with polymorphonuclear leukocytes after removal from the circuit before the adhesion assay. RESULTS: After 60 min of circulation, the neutrophils from NO-treated circuits showed significantly reduced CD11b/CD18 surface expression compared with the control group. There was also a significant reduction in neutrophil-endothelial adhesion in the NO group after 120 min of circulation. Monoclonal antibodies to both CD11b and CD18 significantly inhibited the adhesion of polymorphonuclear leukocytes at endothelial cells after 120 min of circulation. CONCLUSIONS: These results confirm that neutrophil activation occurs during cardiopulmonary bypass. The addition of NO to the circuits of extracorporeal circulation significantly affects neutrophil adhesion to endothelial cells.