Mariateresa Giglio

Goal-directed haemodynamic therapy and gastrointestinal complications in major surgery: a meta-analysis of randomized controlled trials

Postoperative gastrointestinal (GI) dysfunction is one of the most frequent complications in surgical patients. Most cases are associated with episodes of splanchnic hypoperfusion due to hypovolaemia or cardiac dysfunction. It has been suggested that perioperative haemodynamic goal-directed therapy (GDT) may reduce the incidence of these complications in cardiac surgery, and other surgery, but clear evidence is lacking. We have undertaken a meta-analysis of the effects of GDT on postoperative GI and liver complications. A systematic search, using MEDLINE, EMBASE, and The Cochrane Library databases, was performed. Sixteen randomized controlled trials (3410 participants) met the inclusion criteria. Data synthesis was obtained using odds ratio (OR) with 95% confidence interval (CI) by random-effects model. Statistical heterogeneity was assessed by Q and I2 statistics. GI complications were ranked as major (required radiological or surgical intervention or life-threatening condition) or minor (no or only pharmacological treatment required). Major GI complications were significantly reduced by GDT when compared with a control group (OR, 0.42; 95% CI, 0.27-0.65). Minor GI complications were also significantly decreased in the GDT group (OR, 0.29; 95% CI, 0.17-0.50). Treatment did not reduce hepatic injury rate (OR, 0.54; 95% CI, 0.19-1.55). Quality sensitive analyses confirmed the main overall results. In patients undergoing major surgery, GDT, by maintaining an adequate systemic oxygenation, can protect organs particularly at risk of perioperative hypoperfusion and is effective in reducing GI complications.

The effects of goal-directed fluid therapy based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials

IntroductionDynamic predictors of fluid responsiveness, namely systolic pressure variation, pulse pressure variation, stroke volume variation and pleth variability index have been shown to be useful to identify in advance patients who will respond to a fluid load by a significant increase in stroke volume and cardiac output. As a result, they are increasingly used to guide fluid therapy. Several randomized controlled trials have tested the ability of goal-directed fluid therapy (GDFT) based on dynamic parameters (GDFTdyn) to improve post-surgical outcome. These studies have yielded conflicting results. Therefore, we performed this meta-analysis to investigate whether the use of GDFTdyn is associated with a decrease in post-surgical morbidity.MethodsA systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through September 2013 was conducted. Data synthesis was obtained by using odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) by random-effects model.ResultsIn total, 14 studies met the inclusion criteria (961 participants). Post-operative morbidity was reduced by GDFTdyn (OR 0.51; CI 0.34 to 0.75; P <0.001). This effect was related to a significant reduction in infectious (OR 0.45; CI 0.27 to 0.74; P = 0.002), cardiovascular (OR 0.55; CI 0.36 to 0.82; P = 0.004) and abdominal (OR 0.56; CI 0.37 to 0.86; P = 0.008) complications. It was associated with a significant decrease in ICU length of stay (WMD -0.75 days; CI -1.37 to -0.12; P = 0.02).ConclusionsIn surgical patients, we found that GDFTdyn decreased post-surgical morbidity and ICU length of stay. Because of the heterogeneity of studies analyzed, large prospective clinical trials would be useful to confirm our findings.

Intrathecal combination of ziconotide and morphine for refractory cancer pain: a rapidly acting and effective choice.

Summary A combination of low doses of ziconotide and morphine, administered intrathecally, allows safe and rapid control of oral opioid–refractory malignant pain. ABSTRACT Ziconotide is a nonopioid intrathecal analgesic drug used to manage moderate to severe chronic pain. The aim of this work is to assess the safety and efficacy of intrathecal (IT) combination of ziconotide and morphine in malignant pain refractory to high doses of oral opioids. Patients with malignant pain refractory to high oral opioids doses with a mean visual analogue scale of pain intensity (VASPI) score of ⩾70 mm were enrolled. An IT combination therapy was administered: Ziconotide was started at a dose of 2.4 μg/day, followed by increases of 1.2 μg/day at intervals of at least 7 days, and an initial IT daily dose of morphine was calculated based on its oral daily dose. Percentage change in VASPI scores from baseline was calculated at 2 days, at 7 days, and weekly until the first 28 days. The mean percentage change of VASPI score from baseline was used for efficacy assessment. Safety was monitored based on adverse events and routine laboratory values. Twenty patients were enrolled, with a mean daily VASPI score at rest of 90 ± 7. All had a disseminated cancer with bone metastases involving the spine. The percentage changes in VASPI mean scores from baseline to 2 days, 7 days, and 28 days were 39 ± 13% (95% confidence interval [CI] = 13.61–64.49, P < .001), 51 ± 12% (95% CI = 27.56–74.56, P < .001), and 62 ± 13% (95% CI = 36.03–87.89%, P < .001), respectively. Four patients experienced mild adverse events related to the study drugs. In conclusion, an IT combination of low doses of ziconotide and morphine allows safe and rapid control of oral opioid–refractory malignant pain.

Haemodynamic goal-directed therapy in cardiac and vascular surgery. A systematic review and meta-analysis

In cardiovascular surgery, reduced organ perfusion and oxygen delivery contribute to increased postoperative morbidity and prolonged intensive care unit stay. Goal-directed therapy (GDT), a perioperative haemodynamic strategy aiming to increase cardiac output, is helpful in preventing postoperative complications, but studies in the context of cardiovascular surgery have produced conflicting results. The purpose of the present meta-analysis is to determine the effects of perioperative haemodynamic goal-directed therapy on mortality and morbidity in cardiac and vascular surgery. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched until July 2011. Randomized controlled trials reporting on adult cardiac or vascular surgical patients managed with perioperative GDT or according to routine haemodynamic practice were included. Primary outcome measures were mortality and morbidity. Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by a random effects model. An OR <1 favoured GDT. Statistical heterogeneity was assessed by Q and I(2) statistics. Eleven articles (five cardiac surgery and six vascular procedures), enrolling a total sample of 1179 patients, were included in the analysis. As compared with routine haemodynamic practice, perioperative GDT did not reduce mortality in either cardiac or vascular surgery (pooled OR 0.87; 95% CI 0.37-2.02; statistical power 64%). GDT significantly reduced the number of cardiac patients with complications (OR 0.34; 95% CI 0.18-0.63; P = 0.0006), but no effect was observed in vascular patients (OR, 0.84; 95% CI 0.45-1.56; P = 0.58). Perioperative GDT prevents postoperative complications in cardiac surgery patients, while it has no effect in vascular surgery. The different characteristics and comorbidities of the population enrolled could explain these conflicting results. More trials conforming to the characteristics of low-risk-of-bias studies and enrolling a larger and well-defined population of patients are needed to better clarify the effect of GDT in the specific setting of cardiovascular surgery.

Perioperative goal-directed therapy with uncalibrated pulse contour methods: impact on fluid management and postoperative outcome

Previous meta-analyses suggest that perioperative goal-directed therapy (GDT) is useful to decrease postoperative morbidity. Most GDT studies analysed were done with pulmonary artery catheters, oesophageal Doppler and calibrated pulse contour methods. Uncalibrated pulse contour (uPC) techniques are an appealing alternative but their accuracy has been questioned. The effects of GDT on fluid management (volumes and volume variability) remain unclear. We performed a meta-analysis of randomized controlled trials investigating the effects of GDT with uPC methods on postoperative outcome. The primary endpoint was postoperative morbidity. Fluid volumes and fluid volume variability (standard deviation/mean) over the GDT period were also studied. Nineteen studies met the inclusion criteria (2159 patients). Postoperative morbidity was reduced with GDT (OR 0.46, 95% CI 0.30-0.70, P<0.001). The volume of colloids was higher [weighted mean difference (WMD) +345 ml, 95% CI 148-541 ml, P<0.001] and the volume of crystalloids was lower (WMD -429 ml, 95% CI -634 to -224 ml, P<0.01) in the GDT group than in the control group. However, the total volume of fluid (WMD -220 ml, 95% CI -590 to 150 ml, P=0.25) and the variability of fluid volume (34% vs 33%, P=0.98) were not affected by GDT. The use of GDT with uPC techniques was associated with a decrease in postoperative morbidity. It was not associated with an increase in total fluid volume nor with a decrease in fluid volume variability.

Candida Colonization Index in Patients Admitted to an ICU

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.

Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial

IntroductionCandida prophylaxis in ICU is still a matter of debate. Oral chemoprophylaxis has been advocated to reduce the incidence of Candida colonisation and infection.MethodsWe performed a randomised trial studying a single drug (nystatin) versus control in surgical/trauma ICU patients. Multiple-site testing for fungi was performed in each patient on ICU admission (T0) and subsequently every 3 days (T3, T6, T9, and so forth). The primary evaluation criterion was the time course of the corrected colonisation index.ResultsNinety-nine patients were enrolled. At admission, 69 patients exhibited Candida colonisation: the most frequently colonised body sites were the stomach and the pharynx. The most frequent isolated species was Candida albicans. The corrected colonisation index was similar in the two groups at T0 (P = 0.36), while a significant statistical difference was observed between the treatment and control groups at T6 (median 0.14 and 0.33, respectively; P = 0.0016), at T9 (median 0.00 and 0.28, respectively; P = 0.0001), at T12 (median 0.00 and 0.41, respectively; P = 0.0008), and at T15 (median 0.00 and 0.42, respectively; P < 0.0003). The same results were obtained in the subgroup of patients already colonised at ICU admission.ConclusionThis trial shows that nystatin prophylaxis significantly reduces fungal colonisation in surgical/trauma ICU patients, even if already colonised.Trial registrationClinicalTrials.gov: NCT01495039

A fatal rhino-cerebral zygomycosis in a young woman with latent diabetes mellitus and cerebral blood vessel agenesis.

Rhino-cerebral zygomycosis (RCZ) is an acute rapidly progressive fungal infection usually occurring in patients with diabetes mellitus and ketoacidosis. Patients typically complain of pain located in the facial, nasal or orbital regions, followed by sudden blindness and cranial nerve palsy. Early diagnosis, correction of risk factors, prompt surgical removal and aggressive antifungal therapy are warranted as life-saving treatments. The following report describes a case of a lethal RCZ which occurred in an apparently healthy woman with latent non-decompensated diabetes mellitus and a fetal-type posterior (FTP) circle of Willis.

Perioperative Hemodynamic Optimization to Reduce Acute Kidney Injury and Mortality in Surgical Patients

Acute kidney injury is a serious complication in surgical and critical care patients and carries an increased risk of mortality and additional hospital costs. Hemodynamic optimization to reduce mortality in critically ill patients with or at risk for AKI is supported by high-level evidence. However, several points of debate are still open, including the type of fluid to be used to reach the hemodynamic targets, the inotropic support, the choice of the monitoring tool, as well as of the hemodynamic variables to be targeted, and which subgroup of the high-risk surgical population could benefit most from a goal-directed therapy approach.