Topical clonidine for neuropathic pain in adults.

BACKGROUND: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist that has been used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs has been gaining interest since the beginning of the century, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated for almost 20 years in clinical trials. This is an update of the original Cochrane Review published in Issue 8, 2015. OBJECTIVES: The objective of this review was to assess the analgesic efficacy and safety of TC compared with placebo or other drugs in adults aged 18 years or above with chronic neuropathic pain. SEARCH METHODS: For this update we searched the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid), and Embase (Ovid) databases, and reference lists of retrieved papers and trial registries. We also contacted experts in the field. The most recent search was performed on 27 October 2021. SELECTION CRITERIA: We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in adults with chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. Any discrepancies were resolved by discussion or by consulting a third review author if necessary. Where required, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) with P values. We used Review Manager Web software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model.  The review primary outcomes were: participant-reported pain relief of 50% or greater; participant-reported pain relief of 30% or greater; much or very much improved on Patient Global Impression of Change scale (PGIC); and very much improved on PGIC. Secondary outcomes included withdrawals due to adverse events; participants experiencing at least one adverse event; and withdrawals due to lack of efficacy. All outcomes were measured at the longest follow-up period. We assessed the certainty of evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies in the review (two new in this update), with a total of 743 participants with painful diabetic neuropathy (PDN). TC (0.1% or 0.2%) was applied in gel form to the painful area two to three times daily. The double-blind treatment phase of three studies lasted 8 weeks to 85 days and compared TC versus placebo. In the fourth study, the double-blind treatment phase lasted 12 weeks and compared TC versus topical capsaicin. We assessed the studies as at unclear or high risk of bias for most domains; all studies were at unclear risk of bias for allocation concealment and blinding of outcome assessment; one study was at high risk of bias for blinding of participants and personnel; two studies were at high risk of attrition bias; and three studies were at high risk of bias due to notable funding concerns. We judged the certainty of evidence (GRADE) to be moderate to very low, downgrading for study limitations, imprecision of results, and publication bias. TC compared to placebo There was no evidence of a difference in number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.78 to 1.86; 179 participants; 1 study; low certainty evidence). However, the number of participants with participant-reported pain relief of 30% or greater during longest follow-up period (8 to 12 weeks) was higher in the TC group compared with placebo (RR 1.35, 95% CI 1.03 to 1.77; 344 participants; 2 studies, very low certainty evidence). The number needed to treat for an additional beneficial outcome (NNTB) for this comparison was 8.33 (95% CI 4.3 to 50.0). Also, there was no evidence of a difference between groups for the outcomes much or very much improved on the PGIC during longest follow-up period (12 weeks) or very much improved on PGIC during the longest follow-up period (12 weeks) (RR 1.06, 95% CI 0.76 to 1.49 and RR 1.82, 95% CI 0.89 to 3.72, respectively; 179 participants; 1 study; low certainty evidence). We observed no evidence of a difference between groups in withdrawals due to adverse events and withdrawals due to lack of efficacy during the longest follow-up period (12 weeks) (RR 0.34, 95% CI 0.04 to 3.18 and RR 1.01, 95% CI 0.06 to 15.92, respectively; 179 participants; 1 study; low certainty evidence) and participants experiencing at least one adverse event during longest follow-up period (12 weeks) (RR 0.65, 95% CI 0.14 to 3.05; 344 participants; 2 studies; low certainty evidence).  TC compared to active comparator There was no evidence of a difference in the number of participants with participant-reported pain relief of 50% or greater during longest follow-up period (12 weeks) between groups (RR 1.41, 95% CI 0.99 to 2.0; 139 participants; 1 study; low certainty evidence). Other outcomes were not reported. AUTHORS' CONCLUSIONS: This is an update of a review published in 2015, for which our conclusions remain unchanged. Topical clonidine may provide some benefit to adults with painful diabetic neuropathy; however, the evidence is very uncertain. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine whether it is possible to predict who or which groups of people will benefit from TC.

Perioperative restrictive versus goal-directed fluid therapy for adults undergoing major non-cardiac surgery.

BACKGROUND: Perioperative fluid management is a crucial element of perioperative care and has been studied extensively recently; however, 'the right amount' remains uncertain. One concept in perioperative fluid handling is goal-directed fluid therapy (GDFT), wherein fluid administration targets various continuously measured haemodynamic variables with the aim of optimizing oxygen delivery. Another recently raised concept is that perioperative restrictive fluid therapy (RFT) may be beneficial and at least as effective as GDFT, with lower cost and less resource utilization. OBJECTIVES: To investigate whether RFT may be more beneficial than GDFT for adults undergoing major non-cardiac surgery. SEARCH METHODS: We searched the following electronic databases on 11 October 2019: Cochrane Central Register of Controlled Trials, in the Cochrane Libary; MEDLINE; and Embase. Additionally, we performed a targeted search in Google Scholar and searched trial registries (World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov) for ongoing and unpublished trials. We scanned the reference lists and citations of included trials and any relevant systematic reviews identified. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing perioperative RFT versus GDFT for adults (aged ≥ 18 years) undergoing major non-cardiac surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened references for eligibility, extracted data, and assessed risk of bias. We resolved discrepancies by discussion and consulted a third review author if necessary. When necessary, we contacted trial authors to request additional information. We presented pooled estimates for dichotomous outcomes as risk ratios (RRs) with 95% confidence intervals (CIs), and for continuous outcomes as mean differences (MDs) with standard deviations (SDs). We used Review Manager 5 software to perform the meta-analyses. We used a fixed-effect model if we considered heterogeneity as not important; otherwise, we used a random-effects model. We used Poisson regression models to compare the average number of complications per person. MAIN RESULTS: From 6396 citations, we included six studies with a total of 562 participants. Five studies were performed in participants undergoing abdominal surgery (including one study in participants undergoing cytoreductive abdominal surgery with hyperthermic intraperitoneal chemotherapy (HIPEC)), and one study was performed in participants undergoing orthopaedic surgery. In all studies, surgeries were elective. In five studies, crystalloids were used for basal infusion and colloids for boluses, and in one study, colloid was used for both basal infusion and boluses. Five studies reported the ASA (American Society of Anesthesiologists) status of participants. Most participants were ASA II (60.4%), 22.7% were ASA I, and only 16.9% were ASA III. No study participants were ASA IV. For the GDFT group, oesophageal doppler monitoring was used in three studies, uncalibrated invasive arterial pressure analysis systems in two studies, and a non-invasive arterial pressure monitoring system in one study. In all studies, GDFT optimization was conducted only intraoperatively. Only one study was at low risk of bias in all domains. The other five studies were at unclear or high risk of bias in one to three domains. RFT may have no effect on the rate of major complications compared to GDFT, but the evidence is very uncertain (RR 1.61, 95% CI 0.78 to 3.34; 484 participants; 5 studies; very low-certainty evidence). RFT may increase the risk of all-cause mortality compared to GDFT, but the evidence on this is also very uncertain (RD 0.03, 95% CI 0.00 to 0.06; 544 participants; 6 studies; very low-certainty evidence). In a post-hoc analysis using a Peto odds ratio (OR) or a Poisson regression model, the odds of all-cause mortality were 4.81 times greater with the use of RFT compared to GDFT, but the evidence again is very uncertain (Peto OR 4.81, 95% CI 1.38 to 16.84; 544 participants; 6 studies; very low-certainty evidence). Nevertheless, sensitivity analysis shows that exclusion of a study in which the final volume of fluid received intraoperatively was higher in the RFT group than in the GDFT group revealed no differences in mortality. Based on analysis of secondary outcomes, such as length of hospital stay (464 participants; 5 studies; very low-certainty evidence), surgery-related complications (364 participants; 4 studies; very low-certainty evidence), non-surgery-related complications (74 participants; 1 study; very low-certainty evidence), renal failure (410 participants; 4 studies; very low-certainty evidence), and quality of surgical recovery (74 participants; 1 study; very low-certainty evidence), GDFT may have no effect on the risk of these outcomes compared to RFT, but the evidence is very uncertain. Included studies provided no data on administration of vasopressors or inotropes to correct haemodynamic instability nor on cost of treatment. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence, we are uncertain whether RFT is inferior to GDFT in selected populations of adults undergoing major non-cardiac surgery. The evidence is based mainly on data from studies on abdominal surgery in a low-risk population. The evidence does not address higher-risk populations or other surgery types. Larger, higher-quality RCTs including a wider spectrum of surgery types and a wider spectrum of patient groups, including high-risk populations, are needed to determine effects of the intervention.

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating this syndrome are very limited. There are six main substance groups that cause damage to peripheral sensory, motor and autonomic neurons, which result in the development of CIPN: platinum-based antineoplastic agents, vinca alkaloids, epothilones (ixabepilone), taxanes, proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide). Among them, the most neurotoxic are platinum-based agents, taxanes, ixabepilone and thalidomide; other less neurotoxic but also commonlyused drugs are bortezomib and vinca alkaloids. This paper reviews the clinical picture of CIPN and the neurotoxicity mechanisms of the most common antineoplastic agents. A better understanding of the risk factors and underlying mechanisms of CIPN is needed to develop effective preventive and therapeutic strategies.

Percutaneous techniques versus surgical techniques for tracheostomy.

BACKGROUND: Tracheostomy formation is one of the most commonly performed surgical procedures in critically ill intensive care participants requiring long-term mechanical ventilation. Both surgical tracheostomies (STs) and percutaneous tracheostomies (PTs) are used in current surgical practice; but until now, the optimal method of performing tracheostomies in critically ill participants remains unclear. OBJECTIVES: We evaluated the effectiveness and safety of percutaneous techniques compared to surgical techniques commonly used for elective tracheostomy in critically ill participants (adults and children) to assess whether there was a difference in complication rates between the procedures. We also assessed whether the effect varied between different groups of participants or settings (intensive care unit (ICU), operating room), different levels of operator experience, different percutaneous techniques, or whether the percutaneous techniques were carried out with or without bronchoscopic guidance. SEARCH METHODS: We searched the following electronic databases: CENTRAL, MEDLINE, EMBASE, and CINAHL to 28 May 2015. We also searched reference lists of articles, 'grey literature', and dissertations. We handsearched intensive care and anaesthesia journals, abstracts, and proceedings of scientific meetings. We attempted to identify unpublished or ongoing studies by contacting manufacturers and experts in the field, and searching in trial registers. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials (quasi-RCTs) comparing percutaneous techniques (experimental intervention) with surgical techniques (control intervention) used for elective tracheostomy in critically ill participants (adults and children). DATA COLLECTION AND ANALYSIS: Three authors independently checked eligibility and extracted data on methodological quality, participant characteristics, intervention details, settings, and outcomes of interest using a standardized form. We then entered data into Review Manager 5, with a double-entry procedure. MAIN RESULTS: Of 785 identified citations, 20 trials from 1990 to 2011 enrolling 1652 participants fulfilled the inclusion criteria. We judged most of the trials to be at low or unclear risk of bias across the six domains, and we judged four studies to have elements of high risk of bias; we did not classify any studies at overall low risk of bias. The quality of evidence was low for five of the seven outcomes (very low N = 1, moderate N = 1) and there was heterogeneity among the studies. There was a variety of adult participants and the procedures were performed by a wide range of differently experienced operators in different situations.There was no evidence of a difference in the rate of the primary outcomes: mortality directly related to the procedure (Peto odds ratio (POR) 0.52, 95% confidence interval (CI) 0.10 to 2.60, I² = 44%, P = 0.42, 4 studies, 257 participants, low quality evidence); and serious, life-threatening adverse events - intraoperatively: risk ratio (RR) 0.93, 95% CI 0.57 to 1.53, I² = 27%, P = 0.78, 12 studies, 1211 participants, low quality evidence,and direct postoperatively: RR 0.72, 95% CI 0.41 to 1.25, I² = 24%, P = 0.24, 10 studies, 984 participants, low quality evidence.PTs significantly reduce the rate of the secondary outcome, wound infection/stomatitis by 76% (RR 0.24, 95% CI 0.15 to 0.37, I² = 0%, P < 0.00001, 12 studies, 936 participants, moderate quality evidence) and the rate of unfavourable scarring by 75% (RR 0.25, 95% CI 0.07 to 0.91, I² = 86%, P = 0.04, 6 studies, 789 participants, low quality evidence). There was no evidence of a difference in the rate of the secondary outcomes, major bleeding (RR 0.70, 95% CI 0.45 to 1.09, I² = 47%, P = 0.12, 10 studies, 984 participants, very low quality evidence) and tracheostomy tube occlusion/obstruction, accidental decannulation, difficult tube change (RR 1.36, 95% CI 0.65 to 2.82, I² = 22%, P = 0.42, 6 studies, 538 participants, low quality evidence). AUTHORS' CONCLUSIONS: When compared to STs, PTs significantly reduce the rate of wound infection/stomatitis (moderate quality evidence) and the rate of unfavourable scarring (low quality evidence due to imprecision and heterogeneity). In terms of mortality and the rate of serious adverse events, there was low quality evidence that non-significant positive effects exist for PTs. In terms of the rate of major bleeding, there was very low quality evidence that non-significant positive effects exist for PTs.However, because several groups of participants were excluded from the included studies, the number of participants in the included studies was limited, long-term outcomes were not evaluated, and data on participant-relevant outcomes were either sparse or not available for each study, the results of this meta-analysis are limited and cannot be applied to all critically ill adults.

Topical clonidine for neuropathic pain.

BACKGROUND: Clonidine is a presynaptic alpha-2-adrenergic receptor agonist used for many years to treat hypertension and other conditions, including chronic pain. Adverse events associated with systemic use of the drug have limited its application. Topical use of drugs is currently gaining interest, as it may limit adverse events without loss of analgesic efficacy. Topical clonidine (TC) formulations have been investigated recently in clinical trials. OBJECTIVES: The objectives of this review were to assess the analgesic efficacy of TC for chronic neuropathic pain in adults and to assess the frequency of adverse events associated with clinical use of TC for chronic neuropathic pain. SEARCH METHODS: We searched the Cochrane Register of Studies (CRS) Online (Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE and EMBASE databases, reference lists of retrieved papers and trial registries, and we contacted experts in the field. We performed the most recent search on 17 September 2014. SELECTION CRITERIA: We included randomised, double-blind studies of at least two weeks' duration comparing TC versus placebo or other active treatment in patients with chronic neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors extracted data from the studies and assessed bias. We planned three tiers of evidence analysis. The first tier was designed to analyse data meeting current best standards, by which studies reported the outcome of at least 50% pain intensity reduction over baseline (or its equivalent) without use of the last observation carried forward or other imputation method for dropouts, reported an intention-to-treat (ITT) analysis, lasted eight weeks or longer, had a parallel-group design and included at least 200 participants (preferably at least 400) in the comparison. The second tier was designed to use data from at least 200 participants but in cases in which one of the above conditions was not met. The third tier of evidence was assumed in other situations. MAIN RESULTS: We included two studies in the review, with a total of 344 participants. Studies lasted 8 weeks and 12 weeks and compared TC versus placebo. 0.1%. TC was applied in gel form to the painful area two to three times daily.Studies included in this review were subject to potential bias and were classified as of moderate or low quality. One drug manufacturer supported both studies.We found no top-tier evidence for TC in neuropathic pain. Second-tier evidence indicated slight improvement after the drug was used in study participants with painful diabetic neuropathy (PDN). A greater number of participants in the TC group had at least 30% reduction in pain compared with placebo (risk ratio (RR) 1.35, 95% confidence interval (CI) 1.03 to 1.77; number needed to treat for an additional beneficial outcome (NNTB) 8.33, 95% CI 4.3 to 50). Third-tier evidence indicated that TC was no better than placebo for achieving at least 50% reduction in pain intensity and on the Patient Global Impression of Change Scale. The two included studies could be subject to significant bias. We found no studies that reported other neuropathic pain conditions.The rate of adverse events did not differ between groups, with the exception of a higher incidence of mild skin reactions in the placebo group, which should have no clinical significance. AUTHORS' CONCLUSIONS: Limited evidence from a small number of studies of moderate to low quality suggests that TC may provide some benefit in peripheral diabetic neuropathy. The drug may be useful in situations for which no better treatment options are available because of lack of efficacy, contraindications or adverse events. Additional trials are needed to assess TC in other neuropathic pain conditions and to determine how patients who have a chance to respond to the drug should be selected for treatment.

Coronary artery disease in older adults with congenital heart defects: risk factors and pharmacotherapy.

INTRODUCTION: With advancing age, adults with congenital heart disease (ACHD) are at a higher risk of developing atherosclerotic coronary artery disease (CAD). OBJECTIVES: We aimed to determine the prevalence of CAD, its risk factors, and use of guideline­directed pharmacotherapy among older patients with ACHD.  Patients and methods: We studied all ACHD patients aged 60 years or older hospitalized in our department between the years 2013 and 2020. CAD was defined as a history of acute coronary syndrome or coronary revascularization, or more than 50% diameter stenosis on coronary angiography. Data regarding the underlying heart defect, prevalence of cardiovascular risk factors, and drug prescriptions were collected. RESULTS: A total of 198 patients with known coronary artery status (mean [SD] age, 66.2 [5.3] years; 43.3% men) were included in the analysis. Of them, 54 (27.3%) had CAD. The individuals with CAD were more often men, and they were more likely to have a mild heart defect, dyslipidemia, and a history of hypertension and tobacco use. Multivariable analysis showed that male sex (P = 0.001), dyslipidemia (P = 0.003), and hypertension (P = 0.04) were positive independent predictors of CAD, whereas overweight / obesity was identified as a negative independent predictor (P = 0.04). The proportion of CAD patients on antiplatelet and / or anticoagulant drugs was 92.6%. ß­Blockers were prescribed to 87% of the patients, and a lipid­lowering agent to 96% of the study population. CONCLUSIONS: CAD is common in older patients with ACHD. Our results underline the importance of identification and treatment of modifiable CAD risk factors in individuals with ACHD. The obesity paradox might also play a role in this population. The rate of guideline­recommended pharmacotherapy implementation seems to be satisfactory.

Harder, better, faster, stronger? Retrospective chart review of adverse events of interactions between adaptogens and antidepressant drugs.

Aim: We aimed to systematically evaluate the prevalence and clinical characteristics of adverse events associated with the adaptogens and antidepressant drug interactions in a retrospective chart review. Methodology: A total of 1,816 reports of adverse events were evaluated. Cases were included in the analysis if the pharmacoepidemiological analysis showed the presence of a high probability of a causal relationship between an adaptogen and antidepressant interaction and the occurrence of adverse events. The following data were extracted from the reports: age, sex, antidepressant, plant products containing adaptogens, other concomitant medications, and clinical consequences of the interactions and their possible mechanisms. Results: Adaptogens were involved in 9% of adverse events associated with the concomitant use of antidepressants and other preparations. We identified 30 reports in which side effects presented a causal relationship with the use of antidepressants and adaptogens. Here, we present the list of adaptogens with the corresponding antidepressants and the side effects caused by their interactions: Withania somnifera: reboxetine (testicle pain and ejaculatory dysfunctions), sertraline (severe diarrhea), escitalopram (myalgia, epigastric pain, nausea, vomiting, restless legs syndrome, and severe cough), and paroxetine (generalized myalgia, ophthalmalgia, and ocular hypertension); Eleutherococcus senticosus: duloxetine (upper gastrointestinal bleeding), paroxetine (epistaxis), sertraline (vaginal hemorrhage), and agomelatine (irritability, agitation, headache, and dizziness); Schisandra chinensis: bupropion (arthralgia and thrombocytopenia), amitriptyline (delirium), and fluoxetine (dysuria); Tribulus terrestris: citalopram (generalized pruritus), escitalopram (galactorrhea), and trazodone (psoriasis relapse); Coptis chinensis: mianserin (arrhythmias), mirtazapine (edema of lower limbs and myalgia), and fluoxetine (gynecomastia); Cimicifuga racemosa: mianserin (restless legs syndrome), paroxetine (gynecomastia and mastalgia), and venlafaxine (hyponatremia); Bacopa monnieri: agomelatine (back pain and hyperhidrosis) and moclobemide (myocardial infarction); Gynostemma pentaphyllum: duloxetine (back pain); Cordyceps sinensis: sertraline (upper gastrointestinal bleeding); Lepidium meyenii: mianserin (restless legs syndrome); and Scutellaria baicalensis: bupropion (seizures). Conclusion: Clinicians should monitor the adverse events associated with the concomitant use of adaptogens and antidepressant drugs in patients with mental disorders. Aggregation of side effects and pharmacokinetic interactions (inhibition of CYP and p-glycoprotein) between those medicines may result in clinically significant adverse events.

Predictors of Recovery Following Lumbar Microdiscectomy for Sciatica: A Systematic Review and Meta-Analysis of Observational Studies.

Chronic post-surgical pain is reported by up to 40% of patients after lumbar microdiscectomy for sciatica, a complaint associated with disability and loss of productivity. We conducted a systematic review of observational studies to explore factors associated with persistent leg pain and impairments after microdiscectomy for sciatica. We searched eligible studies in MEDLINE, Embase, and CINAHL that explored, in an adjusted model, predictors of persistent leg pain, physical impairment, or failure to return to work after microdiscectomy for sciatica. When possible, we pooled estimates of association using random-effects models using the Grading of Recommendations Assessment, Development, and Evaluation approach. Moderate-certainty evidence showed that the female sex probably has a small association with persistent post-surgical leg pain (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.63 to 2.08; absolute risk increase (ARI) = 1.8%, 95% CI = -4.7% to 11.3%), large association with failure to return to work (OR = 2.79, 95% CI = 1.27 to 6.17; ARI = 10.6%, 95% CI = 1.8% to 25.2%), and older age is probably associated with greater postoperative disability (ß = 1.47 points on the 100-point Oswestry Disability Index for every 10-year increase from age (>/=18 years), 95% CI = -4.14 to 7.28). Among factors that were not possible to pool, two factors showed promise for future study, namely, legal representation and preoperative opioid use, which showed large associations with worse outcomes after surgery. The moderate-certainty evidence showed female sex is probably associated with persistent leg pain and failure to return to work and that older age is probably associated with greater post-surgical impairment after a microdiscectomy. Future research should explore the association between legal representation and preoperative opioid use with persistent pain and impairment after microdiscectomy for sciatica.

Supplemental perioperative steroids for surgical patients with adrenal insufficiency.

BACKGROUND: Adrenal crisis is a life threatening condition which can be induced by stress during surgery in patients with adrenal insufficiency. This may be prevented by perioperative administration of high doses of steroids. There is disagreement on whether supplemental perioperative steroids are required and, when administered, on the amount and frequency of doses. The review was originally published in 2009 and was updated in 2012. OBJECTIVES: To assess whether it is necessary to administer supplemental perioperative steroids in adult patients on maintenance doses of glucocorticoids because of adrenal insufficiency. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2); MEDLINE (1966 to February 2012); EMBASE (1980 to February 2012); LILACS (1982 to May 2012); and the databases of ongoing trials. We handsearched the Journal of Clinical Endocrinology and Metabolism (1982 to 2008), Clinical Endocrinology (1972 to 2008), Surgery (1948 to 1994), Annals of Surgery (1948 to 1994), and Anaesthesia (1948 to 2001). The original search was performed in January 2009. SELECTION CRITERIA: We included randomized controlled trials that compared the use of supplemental perioperative steroids to placebo in adult patients on maintenance doses of steroids and who required surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for missing information. We used mean differences and standard deviations to summarize the data for each group. MAIN RESULTS: Two trials involving 37 patients were included. These studies reported that supplemental perioperative steroids were not required during surgery for patients with adrenal insufficiency. Neither study reported any adverse effects or complications in the intervention and control groups. Both studies were graded as having a high risk of bias. AUTHORS' CONCLUSIONS: Owing to the small number of patients, the results may not be representative. Based on current available evidence, we are unable to support or refute the use of supplemental perioperative steroids for patients with adrenal insufficiency during surgery.

Use of Continuous Veno-Venous Hemodialysis (CVVHD) in Treatment of a Polytrauma Patient with Severe Hemophilia A.

BACKGROUND There are very few reports in the literature worldwide on how to deliver continuous renal replacement therapy (CRRT) to patients with multi-organ trauma and severe hemophilia A. The aim of this case report is to describe successful multidisciplinary, intensive treatment of a patient with multi-organ trauma suffering from severe hemophilia A with the use of continuous veno-venous hemodialysis with regional citrate anticoagulation (Ci-Ca CVVHD). CASE REPORT We report a case of a 47-year-old man with severe hemophilia A, who had multi-organ trauma as a result of a serious traffic accident and was admitted to the Trauma Centre of Emergency and Disaster Medicine in Krakow, Poland in critical condition. Due to elevated laboratory markers of kidney damage (creatinine 204 mmol/l, glomerular filtration rate (GFR) 32 ml/min/1.73 m²), very high myoglobin level (>1000 µ/l) associated with rhabdomyolysis, oliguria (diuresis <0.5 ml/kg/h), and overhydration as a consequence of massive transfusion of blood products and fluids, on day 2 after the injury Ci-Ca CVVHD was initiated as a part of intensive, multidisciplinary treatment. This approach proved to be successful in our patient as he was discharged from the Intensive Care Unit on day 45 after the injury in good general condition, with stable circulatory and respiratory system, without any apparent neurological deficits, and with good renal function (creatinine 50 mmol/l, GFR >60 ml/min/1.73 m²). CONCLUSIONS Our case report shows that intensive, multidisciplinary treatment with implementation of Ci-Ca CVVHD may be an effective and safe method of care for patients with multi-organ trauma and hemophilia A.

The volume of infusion fluids correlates with treatment outcomes in critically ill trauma patients.

Background: Appropriate fluid management is essential in the treatment of critically ill trauma patients. Both insufficient and excessive fluid volume can be associated with worse outcomes. Intensive fluid resuscitation is a crucial element of early resuscitation in trauma; however, excessive fluid infusion may lead to fluid accumulation and consequent complications such as pulmonary edema, cardiac failure, impaired bowel function, and delayed wound healing. The aim of this study was to examine the volumes of fluids infused in critically ill trauma patients during the first hours and days of treatment and their relationship to survival and outcomes. Methods: We retrospectively screened records of all consecutive patients admitted to the intensive care unit (ICU) from the beginning of 2019 to the end of 2020. All adults who were admitted to ICU after trauma and were hospitalized for a minimum of 2 days were included in the study. We used multivariate regression analysis models to assess a relationship between volume of infused fluid or fluid balance, age, ISS or APACHE II score, and mortality. We also compared volumes of fluids in survivors and non-survivors including additional analyses in subgroups depending on disease severity (ISS score, APACHE II score), blood loss, and age. Results: A total of 52 patients met the inclusion criteria for the study. The volume of infused fluids and fluid balance were positively correlated with mortality, complication rate, time on mechanical ventilation, length of stay in the ICU, INR, and APTT. Fluid volumes were significantly higher in non-survivors than in survivors at the end of the second day of ICU stay (2.77 vs. 2.14 ml/kg/h) and non-survivors had a highly positive fluid balance (6.21 compared with 2.48 L in survivors). Conclusion: In critically ill trauma patients, worse outcomes were associated with higher volumes of infusion fluids and a more positive fluid balance. Although fluid resuscitation is lifesaving, especially in the first hours after trauma, fluid infusion should be limited to a necessary minimum to avoid fluid overload and its negative consequences.

The burden of cardiovascular risk factors among seniors with congenital heart disease: A single tertiary center experience.

BACKGROUND: The number of adults with congenital heart disease (ACHD) surviving to old age is increasing worldwide. Acquired cardiovascular comorbidities may complicate the course and treatment of the underlying congenital disease and worsen the prognosis. AIMS: The study aimed to assess the burden of cardiovascular (CV) risk factors among elderly patients with ACHD. METHODS: A retrospective analysis of data on all patients ≥60 years of age hospitalized in a tertiary clinic for ACHD was performed from July 2013 to March 2020. We collected information on smoking status, body mass index, and the presence of dyslipidemia, systemic hypertension, and diabetes. RESULTS: The most common CV risk factors among 322 patients ≥60 years of age (median age 66 years; 34% men) were: being overweight/obesity (65.5%), dyslipidemia (64.9%), and arterial hypertension (60.6%). Over 21% of patients suffered from diabetes, and 25.8% were smokers. Over 54% of patients had two or 3 CV risk factors. Patients above 70 years of age were healthier in terms of being overweight/obesity, dyslipidemia, and smoking status. Patients with mild ACHD were more likely hypertensive compared to individuals with complex defects. The highest CV burden was noted in younger men with mild ACHD. CONCLUSIONS: We demonstrated a high burden of CV risk factors in seniors with ACHD. Special attention should be paid to the identification and control of classical CV risk factors in order to prevent acquired CV disease in this population.

What to look for in patient with continuous murmur and history of ventricular septal defect?

During diagnostic process it is very important to conduct scrupulous interview and thorough physical examination. Properly interpreted auscultation phenomena allow for appropriate planning of further imaging studies.

Systemic right ventricle in elderly patients with congenitally corrected transposition of the great arteries: Clinical profile, cardiac biomarkers, and echocardiographic parameters.

OBJECTIVE: The number of patients with congenitally corrected transposition of the great arteries (ccTGA) surviving to old age is increasing. This study therefore sought to characterize 'geriatric' systemic right ventricle (sRV) in terms of clinical profile, cardiac biomarkers, and echocardiography-derived function when compared with findings in younger patients. METHODS: A single-center cross-sectional study of adults with ccTGA was performed. Patients underwent clinical assessment; transthoracic echocardiography; and venous blood sampling including N-terminal pro-B-type natriuretic peptide (NTproBNP), galectin-3, and soluble suppression of tumorgenicity 2 (sST2) measurements. In the echocardiographic study, the sRV function was assessed using fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), systolic pulsed-wave Doppler velocity (s'), and longitudinal strain (LS). RESULTS: Ten patients with ccTGA aged 60 years or older and 53 patients younger than 60 years of age were included. There were significantly more individuals with hypertension (40% vs. 5.7%), dyslipidaemia (50% vs. 5.7%), and atrial fibrillation (70% vs. 20.7%) in the older group; similarly, we found higher NTproBNP (2706 pg/mL vs. 784.7 pg/mL; p<0.001), and galectin-3 (10.15 ng/mL vs. 7.24 ng/mL; p=0.007) concentrations in elderly ccTGA individuals, while sST2 content did not vary significantly according to age. Upon echocardiographic assessment, lower sRV FAC (28.6% vs. 36.1%; p=0.028) and LS (-12% vs. -15.5%; p=0.017) values were observed in patients aged 60 years or older. TAPSE and s' did not differ between the age groups. CONCLUSION: Careful screening for acquired comorbidities, particularly atrial fibrillation, in elderly ccTGA patients is warranted. Examining selected cardiac biomarkers and echocardiography-derived parameters are useful in the assessment of the aging sRV.

Perioperative Immunosuppression and Risk of Cancer Progression: The Impact of Opioids on Pain Management.

Opioids comprise an important group of drugs used in cancer pain pharmacotherapy. In recent years, more and more studies have emerged indicating the potentially immunosuppressive effects of opioid analgesics and their serious consequences, including the risk of cancer progression. The identification of these risks has prompted a search for other effective, and most importantly, safer methods of perioperative analgesic management. Regional analgesia techniques, which allow for a significant reduction in opioid dosing and thus diminish the risk of immunosuppression associated with these drugs, seem to offer substantial hope in this respect. A number of studies available in the literature assess the effects of regional analgesia techniques on cancer progression; however, it is often difficult to interpret their results owing to several perioperative factors (such as surgical trauma, inadequate pain and stress relief, and hypothermia) which are also attributed immunosuppressive effects and tend to be implicated in increased risk of cancer progression. Further research is needed to verify the available data on both the potential adverse effects of opioids and the possible protective effects of regional analgesia techniques on cancer patients.

Pharmacotherapy of pain in cancer patients - recommendations of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons.

Guidelines for the pharmacotherapy of pain in cancer patients were developed by a group of 21 experts of the Polish Association for the Study of Pain, Polish Society of Palliative Medicine, Polish Society of Oncology, Polish Society of Family Medicine, Polish Society of Anaesthesiology and Intensive Therapy and Association of Polish Surgeons. During a series of meetings, the experts carried out an overview of the available literature on the treatment of pain in cancer patients, paying particular attention to systematic reviews and more recent randomized studies not included in the reviews. The search was performed in the EMBASE, MEDLINE, and Cochrane Central Register of Controlled Trials databases using such keywords as "pain", "cancer", "pharmacotherapy", "analgesics", and similar. The overviewed articles included studies of pathomechanisms of pain in cancer patients, methods for the assessment of pain in cancer patients, and drugs used in the pharmacotherapy of pain in cancer patients, including non-opioid analgesics (paracetamol, metamizole, non-steroidal anti-inflammatory drugs), opioids (strong and weak), coanalgesics (glucocorticosteroids, α2-adrenergic receptor agonists, NMDA receptor antagonists, antidepressants, anticonvulsants, topical medications) as well as drugs used to reduce the adverse effects of the analgesic treatment and symptoms other than pain in patients subjected to opioid treatment. The principles of opioid rotation and the management of patients with opioidophobia were discussed and recommendations for the management of opioid-induced hyperalgesia were presented. Drugs used in different types of pain experienced by cancer patients, including neuropathic pain, visceral pain, bone pain, and breakthrough pain, were included in the overview. Most common interactions of drugs used in the pharmacotherapy of pain in cancer patients as well as the principles for the management of crisis situations. In the final part of the recommendations, the issues of pain and care in dying patients are discussed. Recommendations are addressed to physicians of different specialties involved in the diagnostics and treatment of cancer in their daily practice. It is the hope of the experts who took part in the development of these recommendations that the recommendations would become helpful in everyday medical practice and thus contribute to the improvement in the quality of care and the efficacy of pain treatment in this group of patients.

Radiofrequency denervation with or without addition of pentoxifylline or methylprednisolone for chronic lumbar zygapophysial joint pain.

Radiofrequency neurolysis of lumbar medial branch is currently the only proven way to treat patients with chronic lumbar zygapophysial joint pain, however, in some patients it can cause transient postoperative pain due to an inflammation caused by trauma of the electrode insertion and the thermal lesion around the target nerves. The aim of this study was to assess the effectiveness of intraoperative injection of methylprednisolone or pentoxifylline in comparison with placebo (saline) to prevent this process. 45 consecutive patients seen by one physician at one pain management clinic were included. Patients were randomly assigned to 3 groups of 15 patients treated with radiofrequency neurotomy procedure with an addition of methylprednisolone, pentoxifylline or saline, respectively, and were observed for 6 months. Pain intensity, summed pain intensity difference, minimum 50% reduction of pain intensity, Patients Satisfaction Score, and local tenderness were determined. The 50% reduction of pain intensity was achieved in 80% of patients one week after the procedure, and at 6 months such results were reported by 60% of patients. There was a significant reduction of pain intensity in all three groups at all time points compared to baseline, however, there were no differences between the three groups. There was a significant difference in local tenderness as a measure of postoperative pain indicating effectiveness of both, methylprednisolone and pentoxifylline. No other complications were noted in any of the patients. Radiofrequency neurotomy is a safe and effective method to treat patients with zygapophysial joint pain. An addition of pentoxifylline and methylprednisolone can reduce postoperative pain commonly appearing within a short time after the procedure, however, neither pentoxifylline nor methylprednisolone influences long-term follow-up results.