Equianalgesia, opioid switch and opioid association in different clinical settings: a narrative review.

Emergency or postoperative pain often represents an authentic challenge in patients who were already on opioid treatment for chronic pain. Thus, their management requires not only the physician's ability to treat acute pain, but also competence in switching the opioid that lost efficacy. Different aspects should be considered, such as opioids titration, switching, association and equianalgesia. The objective of this paper is to provide a narrative review, which has been elaborated and discussed among clinicians through an iterative process involving development and review of the draft during two web-based meetings and via email. This expert opinion aims to facilitate the correct opioid use through appropriate practices with a focus on pain treatment in emergency and postoperative pain. Equianalgesia tables were reviewed and integrated by clinicians and researchers with expertise in anesthesia, postoperative medicine, intensive care, emergency medicine pharmacology and addiction medicine. Special populations (liver/kidney failure, elder, pediatric, pregnancy/lactation) are discussed in detail along with other critical scenarios, such as: (i) rapid pain worsening in chronic pain (aggravating pain due to disease progression or tolerance development to analgesic therapy); (ii) acute pain on maintenance treatment; and (iii) pain management of complicated patients in emergency care. Extended and updated equianalgesia tables and conversion rates for 17 different opioid formulations (of 9 different molecules) are presented as follows. Opioids remain the class that best suits clinical needs of emergency and post-operative medicine. However, it should be stressed that equianalgesia can be affected by drug-to-drug interactions and pharmacological imprecision, in a complex field where clinical experience may be the main guiding principle.

What if COVID-19 affects the child: which weapons and how to use them.

Since the reports in Wuhan (China), in December 2019, of the first cluster of cases of pneumonia caused by the new Coronavirus called 2019-nCoV or SARS-CoV-2, there has been a pandemic spread of the infection. By now, we have no specific therapy to counteract this emergency. The latest epidemiological data suggest that children are just as likely as adults to get infected by the virus. Most of them show mild clinical pictures or are completely asymptomatic, but there is an increased risk for severe disease in infancy (<12 months of age) and in children with underlying medical conditions. In this article, research achievements on the treatment of pediatric SARS-CoV-2 infection are examined.

Sportomics: metabolomics applied to sports. The new revolution?

Sportomics is the application of metabolomics in sports to investigate the metabolic effects of physical exercise on individuals, whether they are professional athletes or not. Metabolomics is one of the "omics" sciences that provide a picture of the metabolic state of a person in physiological or pathological conditions. This is achieved through the analysis of metabolites present in a biological fluid, such as saliva, blood, feces, and urine. The authors revised the recent literature concerning this topic and discussed the useful information that sportomics can provide and the limits of the current experimental settings. Furthermore, in the future, sportomics analyses could be used to prevent and manage injuries as it would be known in advance if an athlete is more prone to experience muscular damage or fatigue. Following more trials, it would also be possible to set the best diet and training programs to get the best performances out of the athletes. Moreover, based on their metabolic profiles, both adults and children could choose tailored physical training in order to preserve and improve their health.

Tapentadol prolonged release in the treatment of musculoskeletal pain: an innovative pharmacological option.

Musculoskeletal pain, encompassing back and osteoarthritis (OA) pain, represents the most frequent source of chronic pain in western countries, and it is particularly frequent in older adults. Remarkably, back and OA pain present, in most cases, both a nociceptive and a neuropathic component of pain. Treatment selection should, therefore, properly consider the ability of a drug to act on both components, reducing the possibility of plastic changes in the central nervous system, and consequently promoting physical rehabilitation. The pharmacological profile of tapentadol, combining synergistically µ-opioid receptor (MOR) agonist and norepinephrine reuptake inhibition (NRI) in one single molecule with a concomitant reduction in the burden of adverse events, is unique, to date, and makes this drug particularly suitable for the treatment of back pain and OA-associated pain, especially when a neuropathic component is present. Tapentadol is an innovative dual-acting analgesic molecule, which combines two mechanisms of action, namely MOR agonism and NRI. This narrative review will briefly discuss the pharmacological action of tapentadol and its rationale for use in back pain and OA.

Risk for Depression, Burnout and Low Quality of Life Among Personnel of a University Hospital in Italy is a Consequence of the Impact One Economic Crisis in the Welfare System?

BACKGROUND: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers. OBJECTIVES: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital. METHOD: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals). RESULTS: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians (i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory. CONCLUSION: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

Controlling catheter-related bloodstream infections through a multi-centre educational programme for intensive care units.

BACKGROUND: Bloodstream infections (BSIs) associated with insertion and maintenance of central venous catheters (CRBSIs) are the most frequent causes of healthcare-associated infections in intensive care units (ICUs). They are responsible for increased length of hospital stay and additional healthcare costs. AIM: To investigate whether an educational programme aimed at healthcare workers resulted in a significant change in the level and trend of infections. METHODS: The research was conducted in five Italian ICUs from July 2012 to August 2014. Surveillance and educational interventions to control infections were applied. Compliance with hand hygiene procedures was assessed via relative risk and 95% confidence interval. Interrupted time-series analysis was used to investigate the change in level and trend of infection during the intervention. FINDINGS: Compliance with hand hygiene procedures improved during the intervention for all staff groups, but physicians showed the lowest compliance rates (nurses from 52.4% to 92.1%; nurse aides from 71.0% to 92%; physicians from 71.0% to 92%; P < 0.001). Significant reductions of 21-55% in CRBSI were observed during the intervention. Small improvements in the monthly infection trend were also observed, but these were not statistically significant. CONCLUSION: An educational programme focusing on general good infection control practice, rather than CVC care bundles, led to a decreased CRBSI rate, even if the improvement was not sustained over time. Continuous performance feedback should be provided to promote long-term adherence to guidelines among all health workers.

A systematic review of the effects of adding neostigmine to local anesthetics for neuraxial administration in obstetric anesthesia and analgesia.

BACKGROUND: Drugs used in obstetric patients must accomplish two goals: efficacy and safety for both mother and fetus. Neostigmine has been co-administered epidurally and intrathecally with local anesthetics and other adjuncts in the obstetric setting. The aim of this meta-analysis was to assess the efficacy and incidence of adverse events related to the use of neostigmine in obstetric anesthesia. METHODS: A meta-analysis of randomized-controlled human trials was conducted using the data sources Google Scholar and PubMed (updated 1 November 2014). Inclusion criteria were: random allocation to treatment; comparison of neostigmine or neostigmine with local anesthetics and/or other adjuvants versus placebo or placebo with local anesthetics and/or other adjuvants; and approval by an ethics committee. RESULTS: The use of neostigmine as an adjuvant in neuraxial anesthesia is associated with a reduction in the dose of local anesthetic during labor analgesia and postoperative analgesia following cesarean section: mean reduction of local anesthetic (ropivacaine or bupivacaine) vs. control -4.08 (95% CI -6.7 to -1.5) mg/h (P=0.002). The risk of nausea was increased vs. control with intrathecal neostigmine (OR 8.99 [95% CI 4.74 to 17.05], P <0.001) but not with epidural neostigmine (OR 0.97 [95% CI 0.46 to 2.05], P=0.94). Use of neuraxial neostigmine was associated with a decrease in the risk of pruritus but there was no increase in the incidence of hypotension, dizziness or sedation and no effect on the incidence of abnormal fetal heart rate patterns or Apgar scores. CONCLUSIONS: Neuraxial administration of neostigmine significantly reduces local anesthetic consumption without serious adverse side effects to the mother or fetus. However, neostigmine is only recommended for epidural administration as intrathecal use significantly increases the incidence of maternal nausea and vomiting.

Pituitary apoplexy after laparoscopic surgery: a case report.

The occurrence of unprobable adverse events during laparoscopic surgery has increased over the years. Among them, pituitary apoplexy has been reported only twice. The increase in the abdominal pressure might play a role in the pituitary apoplexy, as well as hemodynamic instability, anticoagulant drugs and air-embolism due to insufflation of CO2 during pneumoperitoneum. We report a case of pituitary apoplexy during laparoscopic resection of sigmoid colon.

Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better.

Perinatal asphyxia is attributed to hypoxia and/or ischemia around the time of birth and may lead to multiorgan dysfunction. Aim of this research article is to investigate whether different metabolomic profiles occurred according to oxygen concentration administered at resuscitation. In order to perform the experiment, forty newborn piglets were subjected to normocapnic hypoxia and reoxygenation and were randomly allocated in 4 groups resuscitated with different oxygen concentrations, 18%, 21%, 40%, and 100%, respectively. Urine metabolic profiles at baseline and at hypoxia were analysed by (1)H-NMR spectroscopy and metabolites were also identified by multivariate statistical analysis. Metabolic pathways associations were also built up by ingenuity pathway analysis (IPA). Bioinformatics analysis of metabolites characterized the effect of metabolism in the 4 groups; it showed that the 21% of oxygen is the most "physiological" and appropriate concentration to be used for resuscitation. Our data indicate that resuscitation with 21% of oxygen seems to be optimal in terms of survival, rapidity of resuscitation, and metabolic profile in the present animal model. These findings need to be confirmed with metabolomics in human and, if so, the knowledge of the perinatal asphyxia condition may significantly improve.

Linezolid-induced thrombocytopenia in impaired renal function: is it time for a dose adjustment? A case report and review of literature.

PURPOSE: Thrombocytopenia is a common complication in the intensive care unit (ICU), but the incidence of drug-induced thrombocytopenia (DIT) is not well defined. We investigate linezolid-induced thrombocytopenia in patients with impaired renal function. Since recent studies suggest that linezolid clearance is reduced in these patients and there are no precise data confirming that dose-adjustment should be required, we performed a systematic analysis in order to establish whether it is necessary to consider a dose adjustment and promote studies to confirm this concept. METHODS: We report a case of thrombocytopenia (nadir 32 × 10(3)/µl) in a patient with acute kidney injury who was treated with linezolid for a MRSA pulmonary infection. We performed a systematic review of the literature through PubMed with the aim to include every case report, case series, prospective and retrospective clinical study reporting linezolid-induced thrombocytopenia with concomitant impaired renal function. RESULTS: An increasing number of clinical studies suggest a correlation between the onset of linezolid-induced thrombocytopenia and renal dysfunction. Close monitoring of platelet count and hemoglobin is recommended in patients treated with linezolid, especially in those with impaired renal function because the reduction of its clearance causes drug accumulation, as some studies have reported. CONCLUSIONS: Clinicians should consider the potential risk of this complication, especially in elderly patients with end-stage renal disease. Further studies should be encouraged to determine if the incidence of linezolid-related thrombocytopenia could be reduced by a dose adjustment according to renal function, for which currently there is still no specific recommendation.

Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery.

BACKGROUND: Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival. METHODS: We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012). RESULTS: We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA. CONCLUSIONS: Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.

Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review.

BACKGROUND: Metformin is known to be rarely associated with lactic acidosis, a serious condition with a poor prognosis. AIM: To review the National Pharmacovigilance Network of the Italian Medicines Agency reporting cases of metformin-associated lactic acidosis. MATERIALS AND METHODS: The National Pharmacovigilance Network of the Italian Medicines Agency, was searched for cases of lactic acidosis that occurred in a 10 years period (from November 2001 to October 2011). Data were analyzed, to identify associated clinical features. A systematic literature research was performed to identify other large case series on metformin associated lactic acidosis. RESULTS: Metformin was the antidiabetic drug most frequently associated with lactic acidosis in the assessed period. Metformin-associated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority (18.2% of all 650 adverse drug reactions reported). There were 59 cases of metformin-associated lactic acidosis (mortality rate of 25.4%). In most patients (89.8%) there was at least one risk factor for the occurrence of lactic acidosis. The predictors of death were low arterial blood pH and absence of acute renal failure. The systematic research of the literature identified only six case-series with more than 30 patients. CONCLUSIONS: This is the second largest case series ever reported on metformin-associated lactic acidosis. We confirmed that this rare complication of metformin is frequently fatal. Death can be predicted when the patient arrive in the hospital with low pH and, not intuitively, if the patient has no acute kidney injury. Risk minimisation measures taken at national level to prevent this serious complication are described.

Is target opioid therapy within sight?

Control of pain has a central role in patients treatment either in advanced cancer or other terminal illnesses and in acute postsurgical or chronic non-malignant diseases. Hospitals should promote programs of research on genetic mechanism, and also biochemical and physiological aspects of pain through highly specialized labs. Opioids are the first choice drugs for moderate to severe chronic pain, especially at the end of life, and among them oral morphine is worldwide recognized by the World Health Organization and by the European Association for Palliative Care as the conventional therapy. Although this general agreement, administration of this class of drugs may be a major medical challenge due to the high effects' variability related to pharmacokinetic and pharmacodynamic parameters, such as absorption, distribution and metabolism, as well as intrinsic efficacy at the receptors involved. For such a reason, optimization of the management regime is not always reached in all the patients. Up to now no one can easily predict which patient will experience side effects or an inadequate pain control. The growing body of evidence concerning a sound genetic background of this human intervariability has prompted research on the field of a personalized therapy, focusing on single nucleotide polymorphisms (SNPs), being the most common and diffuse form of genetic variation. This review has the main goal to report the most promising human genetic polymorphisms involved in opioid treatment, and address the relationship between these polymorphisms and the clinical outcome.

Acute nephrotoxicity of NSAID from the foetus to the adult.

NSAIDs are generally considered to be safe and well tolerated, but, even with the advent of selective COX-2 inhibitors, nephrotoxicity remains a concern. An impaired renal perfusion caused by the inhibition of prostaglandin synthesis is claimed like the more frequent cause of an acute renal failure due to NSAIDs, while a chronic interstitial nephritis or an analgesic nephropathy are believed the causes of a chronic renal failure. The real incidence of renal side effects of NSAIDs is still unclear and it differs between the age of the patients and the reports present in the literature. The occurrence of renal side effects following prenatal exposure to NSAIDs seems to be rare considering the large number of pregnant woman treated with indomethacin or other prostaglandin inhibitors. NSAID-related nephrotoxicity remains an important clinical problem in the newborns, in whom the functionally immature kidney may exert a significant effect on the disposition of the drugs. Instead, nephrotoxicity is a rare event in children and the risk is lower than adults. In healthy adult patients the incidence of renal adverse effects is very low, less than 1%. The risk increased with age. The elderly are at higher risk, and it is correlated at the presence of pretreatment renal disease, hypovolemia due to use of diuretics, diabetes, congestive heart failure or alteration of NSAID pharmacokinetics.

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.

The role of neurolytic celiac plexus block in the treatment of pancreatic cancer pain.

Pancreatic carcinoma, an important leading cause of cancer death, has increased steadily in incidence and still has a poor prognosis. Pain is one of the most frequent symptoms, affecting more than 75% of patients. It is often present in the early stages of disease and may be severe and difficult to treat. Abdominal viscera, including pancreas, liver, gallbladder, adrenal, kidney, and the gastrointestinal tract from the level of the gastroesophageal junction to the splenic flexure of the colon are innervated, at least in part, via the celiac plexus. Thus, painful tumors in these viscera may have pain relieved through the use of a neurolytic celiac plexus block (NCPB). Although some investigators questioned the role and the efficacy of NCPB in the treatment of upper abdominal cancer pain, most of them have suggested that it may represent the optimal treatment, especially for pancreatic cancer pain. In this report we have reviewed the techniques, results, and complications of NCPB for the treatment of pancreatic cancer pain.