Effects of hydrogen sulfide (H2S) on mesenteric perfusion in experimental induced intestinal ischemia in a porcine model.

INTRODUCTION: Insufficient mesenteric perfusion is a dramatic complication in critically ill patients. Hydrogen sulfide, a newly recognized endogenous gaseous mediator, acts as an intestinal vasoactive agent and seems to protect against mesenteric ischemic damage. We investigated whether sodium hydrogen sulfide, a hydrogen sulfide donor, can improve mesenteric perfusion in an experimental model of pigs, both in physiological and ischemic conditions. METHODS: The study was conducted at Careggi University Hospital (Florence, IT). Fourteen male domestic pigs (≈10 Kg) were anesthetized and mechanically ventilated. Animals were randomized in control and ischemia groups. Mesenteric ischemia was induced with a positive end-expiratory pressure of 15 cmH2O. After mini-laparotomy, each animal received incremental doses of sodium hydrogen sulfide every 20 minutes. Perfusion of both the jejunal mucosa and sternal skin were measured by laser Doppler flowmeter, and systemic hemodynamic parameters were monitored. RESULTS: In the control group, sodium hydrogen sulfide was able to significantly improve the mesenteric perfusion, showing a 50% increase from the baseline blood flow. In the ischemia group, NaHS-induced a two-fold increase of the mesenteric post-ischemic perfusion with a recovery up to 70% of pre- positive end-expiratory pressure mesenteric blood flow. Sodium hydrogen sulfide did not directly or indirectly (by blood flow redistribution) affect the sternal skin microcirculation, heart rates, or mean arterial pressure, suggesting a tissue-specific micro-vascular action. CONCLUSIONS: In a porcine model, we observed a mesenteric perfusion recovery mediated by administration of hydrogen sulfide donor without affecting general hemodynamic.

Implementation and preliminary validation of a new score that predicts post-operative complications.

BACKGROUND: An accurate pre-operative risk assessment could reduce morbidity and mortality for high-risk surgical patients. The aim of the study was to implement and preliminary validate a new score that could predict the occurrence of post-operative complications (PoCs): the Anesthesiological and Surgical Postoperative Risk Assessment (ASPRA) score. METHODS: The ASPRA score was created through a literature's review; a score of 1-3 was given to each identified risk factor, according to its statistical correlation with PoC. ASPRA was retrospectively applied to a derivation set of 176 surgical patients. A receiver operating characteristic (ROC) analysis evaluated the discriminating ability of the score and cutoff value in predicting the occurrence of PoCs, according to the Clavien-Dindo classification of surgical complications. The statistical validation of the score and related cutoff values was prospectively ran within a validation set of 1928 surgical patients. RESULTS: Through ROC analysis, an ASPRA score of 7 was chosen as the cutoff value in the derivation set. In the validation set, 65.3% of patients presented a PoC (Clavien ≥ 1). In this group, ROC analysis showed an area under the curve (AUC) of 0.72, and although potentially related to the high rate of complications a high positive predictive value of 87.0% has been observed. No significant differences were found in ROC-AUC, sensitivity, specificity, or positive or negative predictive value between the derivation and validation sets (P > 0.05). CONCLUSION: The new ASPRA score has a high positive predictive value to predict the occurrence of PoCs. Further prospective studies are required to confirm these results.

Cardiorenal syndromes and sepsis.

The cardiorenal syndrome is a clinical and pathophysiological entity defined as the concomitant presence of renal and cardiovascular dysfunction. In patients with severe sepsis and septic shock, acute cardiovascular, and renal derangements are common, that is, the septic cardiorenal syndrome. The aim of this paper is to describe the pathophysiology and clinical features of septic cardiorenal syndrome in light of the actual clinical and experimental evidence. In particular, the importance of systemic and intrarenal endothelial dysfunction, alterations of kidney perfusion, and myocardial function, organ "crosstalk" and ubiquitous inflammatory injury have been extensively reviewed in light of their role in cardiorenal syndrome etiology. Treatment includes early and targeted optimization of hemodynamics to reverse systemic hypotension and restore urinary output. In case of persistent renal impairment, renal replacement therapy may be used to remove cytokines and restore renal function.

Postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF) is common among surgical patients and associated with a worse outcome. Pathophysiology of POAF is not fully disclosed, and several perioperative factors could be involved. Direct cardiac stimulation from perioperative use of catecholamines or increased sympathetic outflow from volume loss/anaemia/pain may play a role. Metabolic alterations, such as hypo-/hyperglycaemia and electrolyte disturbances, may also contribute to POAF. Moreover, inflammation, both systemic and local, may play a role in its pathogenesis. Strategies to prevent POAF aim at reducing its incidence and ameliorate global outcome of surgical patients. Nonpharmacological prophylaxis includes an adequate control of postoperative pain, the use of thoracic epidural analgesia, optimization of perioperative oxygen delivery, and, possibly, modulation of surgery-associated inflammatory response with immunonutrition and antioxidants. Perioperative potassium and magnesium depletion should be corrected. The impact of those interventions on patients outcome needs to be further investigated.

Cefazolin bolus and continuous administration for elective cardiac surgery: improved pharmacokinetic and pharmacodynamic parameters.

OBJECTIVE: Cefazolin (1-2 g bolus at induction possibly repeated after cardiopulmonary bypass) remains the standard for antibiotic prophylaxis in cardiac surgery. Data indicate, however, that it is underdosed with this dosing schedule. A prospective, randomized study comparing intermittent versus loading dose plus continuous infusion for the same total dose of cefazolin was performed to assess which modality is pharmacokinetically and pharmacodynamically advantageous. METHODS: Patients received 2 g cefazolin as a starting dose and then were divided into an intermittent group (receiving another 1 g at 3, 9, and 15 hours after the first dose) and a continuous group (continuous infusion started after the first dose, providing 1 g every 6 hours for 18 hours). Cefazolin levels were measured in blood and atria. RESULTS: Mean total and calculated free trough concentrations in blood varied greatly among patients in the intermittent group and were lower than those in the continuous group (P < .05 at 15, 18 and 24 hours). For 9 of 10 (90%) patients in the continuous infusion group, the targeted pharmacokinetic and pharmacodynamic goal (time above minimal inhibitory concentration >90%) was achieved, whereas the goal was met for only 3 of 10 (30%) in the intermittent group (P < .05). The mean atrial tissue concentration was also higher with continuous infusion (P < .05). CONCLUSIONS: Administration of cefazolin as bolus plus continuous infusion has pharmacokinetic and pharmacodynamic advantages relative to intermittent administration. It provides more stable serum levels, lower interpatient variability, and higher myocardial tissue penetration.

Propofol sedation in a colorectal cancer screening outpatient cohort.

AIM: Colorectal cancer screening colonoscopies require sedation for both anxiety and pain. Propofol is used worldwide and allows for rapid and profound sedation with quick recovery after cessation of infusion. However, there is still a debate about whether it should be administered by anesthetists, gastroenterologists, or trained nurses. The aim of the study was to assess the number and proportion of patients who might benefit from the quality and safety of sedation under propofol during colonoscopies in a cohort of colorectal cancer screening outpatients. METHODS: Patients' genders, ages, numbers of operative procedures, and prior experience with colonoscopies were recorded, and differences were tested between sedated and unsedated patients. The need for mask ventilation and the rate of anesthetically, medically, or surgically related complications were compared between sedated and unsedated patients. The number of complete colonoscopies, length of the procedures, and time to reach the ileocecal valve were compared between sedated and unsedated patients. RESULTS: Of 135 colonoscopies, 101 were performed under sedation. All sedated patients underwent complete endoscopic examinations, while 8.9% of unsedated patients had their examination stopped due to excessive discomfort or pain. Colonoscopies tended to be shorter in sedated than unsedated patients. No anesthesia-related complications occurred. In 3/135 patients, a short period (<3 min) of mask ventilation was necessary. One surgical complication occurred among the sedated patients. One unsedated patient suffered a medical complication (dyspnea and ST-T elevation). CONCLUSIONS: Propofol sedation can be safely applied to colorectal cancer screening outpatients. Sedation was managed by a dedicated anesthetic staff and no patient suffered anesthesia-related complications.

Acute severe arterial hypertension: therapeutic options.

Arterial hypertension is a very common condition. Cerebral, coronary and renal vessels are mainly affected by the deleterious effect of this condition, and both acute and chronic organ failure may ensue. Exacerbation of underlying pathophysiologic conditions or new precipitating factors can lead to hypertensive crisis, either urgencies or emergencies. During hypertensive emergencies, a quick raise in arterial pressure may lead to acute and significant organ dysfunction, such as aortic dissection, acute myocardial infarction, intracranial bleeding or acute renal failure. Perioperative hypertension often takes the shape of a crisis and it can be related to hypothermia, pain, neuro-hormonal response to surgical trauma or antihypertensive drugs withdrawal. Treatment for hypertensive crisis should achieve a progressive control of blood pressure, avoiding any abrupt decrease in organ blood supply. Therapeutic options are many and different in terms of pharmacokinetics and pharmacodynamic profiles. The best option should be based upon the characteristics of the patient and the pathophysiology of the hypertensive crisis. Of particular interest, some agents are metabolized by blood esterase and have a very short half life (e.g., clevidipine). This allows tight titration of their effect, which is advisable when carefully lowering blood pressure. This is of particular importance when treating hypertensive crisis in surgical patients both intra-operatively or in critical care.

Pathophysiology of sepsis in the elderly: clinical impact and therapeutic considerations.

The aging world population will increase the incidence and mortality of severe sepsis. The aim of the present article is to review the pathophysiological differences in sepsis and its clinical impact on the elderly. The impact of immunosenescence on innate and acquired immunity is associated with relative immunologic depression that may favor the spreading of inflammation. Elderly patients also have enhanced apoptotic pathways that may contribute to the incidence of mortality due to sepsis. The inflammation-coagulation network is activated by age, explaining the success of some specific therapies. The initial clinical picture of sepsis in the elderly may be ambiguous but the specific pathopysiological changes of aging increase the risk of a sudden deterioration to severe sepsis with the development of a serious cardiovascular dysfunction. The reduced stress tolerance characteristic of aged tissues explains the high incidence of multi-organ failure in such patients. The specific pathophysiological and clinical picture of sepsis underlies the increased mortality in such patients and prompts research on therapeutic strategies with particular benefits to elderly septic patients.

Bispectral Index compared to Ramsay score for sedation monitoring in intensive care units.

AIM: Continuous monitoring is of paramount importance in order to obtain a correct level of sedation in ICU patients. Clinical scoring systems, although simple and inexpensive, are often inadequate in evaluating the patient level of consciousness. Among instrumental tools for sedation monitoring, Bispectral Index (BIS) is now widely used due to its reliability and applicability. Nevertheless some doubts still exist regarding its usefulness in ICU. METHODS: Sedation, obtained with propofol or midazolam, was monitored with Ramsay scale and BIS in 40 patients admitted in ICU for postoperative monitoring after major abdominal or vascular surgery. A correlation between Ramsay score and BIS values was searched using Pearson test. RESULTS: A good correlation between Ramsay score and BIS values was observed. At the deeper levels of sedation a wide range of BIS values corresponds to Ramsay score 6, indicating various levels of central nervous system depression that are not identified by clinical evaluation. CONCLUSIONS: BIS monitoring is useful in ICU patients and allows a finest differentiation of sedation level in deeply sedated ICU patients.