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.

Italian Intersociety Recommendations on pain management in the emergency setting (SIAARTI, SIMEU, SIS 118, AISD, SIARED, SICUT, IRC).

BACKGRAUND: Pain is the primary reason for admission to the Emergency Department (ED). However, the management of pain in this setting is often inadequate because of opiophagia, fear of excessive sedation, and fear of compromising an adequate clinical assessment. METHODS: An intersociety consensus conference was held in 2010 on the assessment and treatment of pain in the emergency setting. This report is the Italian Intersociety recommendations on pain management in the emergency department setting. RESULTS: The list of level A recommendations includes: 1) use of IV acetaminophen for opioid sparing properties and reduction of opioid related adverse events; 2) ketamine-midazolam combination preferred over fentanyl-midazolam fentanyl-propofol in pediatric patients; 3) boluses of ketamine IV (particularly in the population under the age of 2 years and over the age of 13) can lead to impairment of the upper airways, including the onset of laryngospasm, requiring specific expertise and skills for administration; 4) the use of ketamine increases the potential risk of psychomotor agitation, which can happen in up to 30% of adult patients (this peculiar side effect can be significantly reduced by concomitant systemic use of benzodiazepines); 5) for shoulder dislocations and fractures of the upper limbs, the performance of brachial plexus block reduces the time spent in ED compared to sedation; 6) pain relief and the use of opioids in patients with acute abdominal pain do not increase the risk of error in the diagnostic and therapeutic pathway in adults; 7) in newborns, the administration of sucrose reduces behavioural responses to blood sampling from a heel puncture; 8) in newborns, breastfeeding or formula feeding during the procedure reduces the measures of distress; 9) in pediatric patients, non-pharmacological techniques such as distraction, hypnosis and cognitive-behavioural interventions reduce procedural pain caused by the use of needles; 10) in pediatric patients, preventive application of eutectic mixtures of prilocaine and lidocaine allows arterial and venous samples to be taken in optimum conditions; 11) in pediatric patients, the combination of hypnotics (midazolam) and N2O is effective for procedural pain, but may be accompanied by loss of consciousness. CONCLUSION: The diagnostic-therapeutic pathway of pain management in emergency should be implemented, through further interdisciplinary trials, in order to improve the EBM level of specific guidelines.

Intracranial haemorrhage in patients on antithrombotics: clinical presentation and determinants of outcome in a prospective multicentric study in Italian emergency departments.

BACKGROUND: Intracranial haemorrhage (ICH) is the type of stroke associated with the highest death rate, and about 30% of ICH occurs in patients on antithrombotic treatment. This study relates clinical presentations and outcome of ICH patients on oral anticoagulant (OA) or antiplatelet (AP) therapy admitted to 33 Italian emergency departments (ED). METHODS: Consecutive patients were enrolled after cranial computed tomography (CT). Primary outcome was the Modified Rankin Scale (MRS) score at 3 months of follow-up. Common descriptive statistics were computed after stratification for traumatic or spontaneous ICH and identification of the anatomical location of bleeding. Multivariate logistic regression was used to assess predictors of death. RESULTS: We recruited 434 patients on AP therapy and 232 on OA. There were 432 spontaneous and 234 traumatic ICH patients. The proportions of AP and OA patients undergoing neurosurgery were 21.8 and 19.4%, respectively, while < 30% underwent procoagulant medical treatment. At the 3-month follow-up, the case fatality rate was 42.0%, while disability or death (MRS 3-6) was 68.1%. The odds ratio for death in OA versus AP patients was 2.63 (95% CI 1.73-4.00) in the whole population and 2.80 (95% CI 1.77-4.41) in intraparenchymal event patients. Glasgow Coma Scale, age, spontaneous event and anticoagulant use were found to be predictors of death both in traumatic and spontaneous events. CONCLUSION: This study confirms the high prevalence of death or disability in OA and AP patients with ICH. As far as the determinants of mortality and disability are concerned, the results of this study might be useful in the clinical management and allocation of resources in the ED setting. The observed low use of procoagulant therapy highlights the need for ED educational programmes to heighten the awareness of available and effective haemostatic treatments.

Role of chronic atrophic gastritis of the body-fundus and achlorhydria in the development of epithelial dysplasia and gastric carcinoma.

BACKGROUND/AIM: Chronic atrophic gastritis of the body-fundus with hypo-achlorhydria has been long since considered the precursor of gastric cancer (GC). A study has been made about the histological pattern of the body-fundic mucosa (oxyntic area) in course of preneoplastic lesions (epithelial dysplasia), associated or progressed to gastric cancer, in order to evaluate the real association with chronic atrophic gastritis and, therefore, with a reduced acid secretion. METHODOLOGY: The study of the histological condition of the body-fundic mucosa and of the acid secretion has been effected in 120 cases of epithelial dysplasia (ED) from January 1990 to November 1997. The casuistry is composed of 70 cases of low grade dysplasia (LGD) and 50 cases of high grade dysplasia (HGD). Gastric biopsy specimens were studied for dyspepsia: for each patient, at least 8 specimens were obtained from the lesion area and in surrounding areas. Besides, at least 4 biopsies have been performed in the opposite gastric region. ED diagnosis was effected according to well defined criteria. The histological study of gastric mucosa in gastritis was effected or revised in accordance with the updated Sydney system (Houston). Stimulated acid secretion was expressed as Maximal Acid Output (MAO), which is the amount of HCl produced in one hour, following stimulation with pentagastrin (6 micro-g/kg). The clinical outcome subdivision of ED was made using the criteria of Rugge et al. (12). RESULTS: HGD significantly associates with GC in comparison with LGD. The histological evaluation of the oxyntic area shows severe chronic atrophic gastritis (SCAG) in a low percentage of cases (15/120: 12.5%): LGD 9/70: 12.85% ; HGD 6/50: 12%. Complete achlorhydria has been noted in 5 cases of LGD and in 1 case of HGD only. In case of GC (43 subjects) SCAG has been evidenced in 10 cases and complete achlorhydria in 5 cases. CONCLUSIONS: From the data of the present experience emerges that the presence of SCAG of the oxyntic area in course of ED or early GC is limited to a low percentage of cases. Such concepts induce to modify some indications related to the endoscopic surveillance and, in accordance with the American Society of Gastrointestinal Endoscopy we are stating that there are no sufficient data to support subsequent endoscopic surveillance for the subjects with atrophic gastritis.

p53 and Ki-67 expression in epithelial gastric dysplasia and in gastric cancer.

BACKGROUND: The aim of this study was to examine p53 and Ki-67 expression in relation to high grade dysplasia (HGD) clinical behaviour. METHODS: A retrospective, cross sectional study was conducted on mucosal biopsies from the stomach of 38 consecutive cases of HGD (25 males, average age: 57.5). The studied samples are represented by gastric biopsies obtained in course of gastroscopy for dyspepsia (at least 8 biopsies). HGD diagnosis was done by experienced pathologists (MC, DG) according to Goldstein's criteria. There were 12 non-dysplastic controls (7 males, average age: 49.4). The immunohistochemical study has been led with the utilization of a p53-antibody. For the cell proliferation assay, the sections were incubated with the MM1 monoclonal antibody. The clinical outcome subdivision of HGD was effected using the criteria of Rugge et al. For the classification of gastric cancer (GC): UICC TNM. RESULTS: p53 positivity has been evidenced in 65.5% of cases, while hyperproliferation in 100% of cases. That independently of the clinical behaviour. CONCLUSIONS: p53 positivity has been found only in part of the HGD cases and moreover a number of HGD with low or absent p53 scores has been found associated with high proliferation indices independently of the clinical evolution. This dissociation of cell kinetics and p53 expression suggests that other genetic events contributing to unregulate cell proliferation may occur in these lesions.

Helicobacter pylori influence on gastric acid secretion in duodenal ulcer patients diagnosed for the first time.

BACKGROUND: Many experiences have hypothesised that Helicobacter pylori induced hypergastrinemia could lead to an increase of the parietal cell mass and, consequently, of acid secretion. METHODS: The parietal cell mass and maximal acid output have been studied in patients with duodenal ulcer diagnosed for the first time, not due to drugs assumption. In particular, it has been evaluated the parietal cell mass and the acid secretion subdividing duodenal ulcer patients in relation to gastrinemia values (hypergastrinemia and normogastrinemia). RESULTS: The parietal cell mass and the maximal acid output remain high independently of Helicobacter pylori presence. About 60% of the subjects in the Helicobacter pylori positive group show gastrinemia values higher than the average: neither did the study reveal in this group any variations in the parietal cell mass and acid secretion. CONCLUSIONS: It emerges from the results that the mild chronic hypergastrinemia in Helicobacter pylori positive duodenal ulcer is not important enough to induce an increase in parietal cell mass and acid secretion. Therefore, Helicobacter pylori eradication is important in relapse prevention of duodenal ulcer, but not for its repercussions on the gastric secretion.

Nocturnal gastric acidity pattern in gastro-oesophageal reflux disease with or without oesophagitis.

The reasons why few patients with gastro-oesophageal reflux disease develop oesophagitis are not yet clear. One of the factors whose role is still debatable is the gastric acid secretory state. The aim of this study was to evaluate whether differences exist in nocturnal gastric acidity between patients with oesophagitis and refluxers without oesophageal lesions. We studied 65 patients with gastro-oesophageal reflux disease, 37 of whom presented erosive oesophagitis, while 28 had no oesophageal lesions. Thirty-one healthy volunteers were used as controls. In both patients and controls intragastric and intraoesophageal pH were measured continuously using 2 in-dwelling glass electrodes, placed in the gastric corpus and in the oesophagus. Mean intragastric pH was calculated over 3 nocturnal time periods: 11.00 p.m.-07.00 a.m.; 11.00 p.m.-03.00 a.m.; 03.00 a.m.-07.00 a.m. Patients with oesophagitis had a lower nocturnal gastric pH (1.6 +/- 0.2) than either refluxers without oesophagitis (2.2 +/- 0.3) (p = 0.05) or controls (2.6 +/- 0.4) (p = 0.02). The difference occurred entirely in the second part of the night. Furthermore, in the same time period, oesophagitis sufferers had a higher percentage of oesophageal acid exposure at pH < 2 (0.7 +/- 0.2) than refluxers without oesophagitis (0.2 +/- 0.1) (p = 0.05), suggesting that gastric findings are of pathogenetic relevance. Patients with reflux oesophagitis have a higher nocturnal intragastric acidity than refluxers without oesophagitis. This difference, confined to the second half of the night, may be due to an altered circadian pattern of gastric acid secretion and may partially explain why only some refluxers develop oesophagitis.

Epidemiology and etiology of "autonomous" nonspecific duodenitis.

In this prospective study we looked for possible epidemiological and etiological factors in "autonomous" nonspecific duodenitis. Of 136 dyspeptic patients who entered the study, duodenitis was found in 25.6% (94.4% chronic duodenitis and 5.6% isolated active duodenitis). Men predominated with a significant prevalence of 74%; 49% of them had white-collar jobs, but age, psychological factors, and the season of the year played no role. We found that smoking and alcohol and coffee intake bore no relation to duodenitis. Helicobacter pylori (HP) was present in only 17.1% of patients with duodenitis, little different from the 10% prevalence in dyspeptic patients without duodenitis. HP was always associated with gastric metaplasia and inflammatory activity.

[The gastric anatomico-functional aspects (parietal cell mass, stimulated acid secretion and gastrinemia) in pernicious anemia]. / Aspetti anatomo-funzionali gastrici (massa cellulare parietale, secrezione acida stimolata e gastrinemia) in corso di anemia perniciosa.

We present here a study of parietal cell mass, stimulated acid secretion and basal gastrinemia both in the course of isolated chronic atrophic gastritis of the body-fundus and in chronic atrophic gastritis of the body-fundus associated with pernicious anemia. Analysis of our results evidences an overlapping cyto-secretory profile characterized by hypoparietalism with hypo-achlorhydria. The higher basal gastrinemia levels in pernicious anemia depend on the histological status of the antral mucosa--which was always normal in the patients with pernicious anemia--rather than any substantial morpho-functional differences of the body-fundus. We thus conclude that the term "atrophic gastritis" should be abolished, and that the term "chronic atrophic gastritis" be used to describe both conditions.

New provocative tests in the diagnosis of esophageal chest pain.

In the present experience, two new provocative tests are proposed in the diagnosis of chest pain. Exertional pHmetry, consisting in a standard ergometric test during esophago-gastric pHmetry, is employed in the diagnosis of chest pain by gastroesophageal reflux. 67 patients with non-cardiac chest pain were submitted to the test: 46 (group A) presenting pain only at rest, and 21 (group B) with exertional or mixed type of pain. Out of group A, 12 (25%) patients presented a positive response (both gastroesophageal reflux and typical pain during exercise). Out of group B, 6 (28.5%) patients responded positively, too. The diagnostic advantage of exertional pHmetry, compared to prolonged pHmetry, amounts to 21.7%. Exertional pHmetry, repeated on the following day, showed that occurrence of gastroesophageal reflux and pain are reproducible in all patients, with occurrence at the same threshold of the first test in 11 (61.1%) out of 18 patients. Endo-esophageal electrical stimulation is employed in the diagnosis of chest pain by motility disturbances: the technique is the same one of cardiological transesophageal atrial pacing. 6 healthy subjects and 21 patients with non-cardiac chest pain negative to other esophageal investigations (7 with and 14 without gastroesophageal reflux disease) were submitted to the test. 9 (43%) out of 21 patients showed a positive response, while in 2 patients (9%) we observed manometric changes without pain, and 10 (48%) showed a negative response. All the control subjects submitted to the test showed a completely negative response.(ABSTRACT TRUNCATED AT 250 WORDS)

Exertional gastroesophageal pH-metry: a new provocative physiological test in the diagnosis of chest pain.

With the aim of determining the value of physical exercise as a provocative test for chest pain associated with gastroesophageal reflux, 67 patients presenting non-cardiac chest pain (normal coronary angiograms and no functional coronary artery alterations) with different characteristics (group A: at rest; group B: exertional or mixed-type) underwent exercise tests during 24-hour gastroesophageal pH-metry associated with electrocardiographic (EKG) monitoring. Thirty-four patients in group A (73.4%), and 12 in group B (57%) showed pathological reflux on 24-hour gastroesophageal pH-metry. Twelve patients in group A (25%) and 6 in group B (28.5%) (total ratio: 26.8%) presented positive responses to exercise, with concomitant occurrence of gastroesophageal reflux, typical pain, without EKG ischemic signals. Exertional pH-metry allowed to reach diagnostic certitude in 10 (14.9%) of 67 patients, 9 presenting 24-hour pH-metry results that only suggested "possible" diagnosis, and 1 without either pathological reflux or pain during prolonged monitoring: all these patients belonged to group A. The repetition of the test showed total reproducibility of the results, with "fixed thresholds" of exercise in 11 of 18 subjects (61.1%). These data suggest the usefulness of grouping different diagnostics (24-hour EKG, pH-metry and exertional test) to increase diagnostic certitude, mainly in patients with primary angina. Exertional pH-metry shows to be an efficacious provocative test, and the only based on a physiological stimulus.

[Esophageal angina]. / Angina esofagea.

Angina-like chest pain, caused by alterations of esophageal function, is an increasingly common occurrence confronting cardiologists: advances in pathogenetic knowledge and in diagnostic possibilities in this field have in fact shed light on the prevalence of esophageal angina, which is present in approximately 60% of patients with angiographically intact coronaries (11% of anginal patients overall). Classically, esophageal chest pain is attributed to alterations of motility or to mucosal disease (pathologic gastro-esophageal reflux of the acid, mixed or alkaline type): this last cause prevails quantitatively. Little is known of the nociceptive mechanisms triggered by these alterations: as far as mucous disease is concerned, activation of the chemosensitive receptors has been postulated, while esophageal mechanoreceptors may be activated, in the course of a motor disorder, by distension of the wall. A recently proposed additional mechanism consists in the induction of parietal esophageal ischemia by chemical or mechanical injury: it is a fascinating and potentially resolvable mechanism, which however requires further investigation. Moreover, elements of psychological nature are also involved in the genesis of esophageal pain. A diagnosis of esophageal angina, heavily conditioned by obvious considerations of prognostic order, must necessarily aim for "certainty". Prolonged monitoring of the endoluminal pH and the adoption of provocative tests, in the course of pH monitoring and manometry, play an important role in achieving this aim (ergometric test, distension induced with a balloon, edrophonium, electrostimulation, seem most effective). A promising outlook is supported by the recent introduction of prolonged manometry. Finally, diagnostic attitude must necessarily abandon its limited specialistic horizon to consider the patient's profile in its entirety.

[Diagnostic evaluation of the patient with esophageal chest pain: our experience]. / Valutazione diagnostica del paziente con dolore toracico esofageo: la nostra esperienza.

Our experience in the field of the "cardio-esophageal" differential diagnosis of angina-like pain derives from the close cooperation between the Divisions of Gastroenterology and Cardiology. Commonly applied tests of esophageal function, always performed during electrocardiographic monitoring, are prolonged gastro-esophageal pH monitoring plus the adoption, as provocative tests, of the stress test in the course pH monitoring, of endo-esophageal distension and of electrostimulation in the course of manometry. An evaluation of prolonged pH monitoring tracings is performed not solely to locate a quantitatively pathological reflux, but especially to identify temporal correlations between the symptoms and the reflux. This explains how we were able to relate pain to reflux in 63% of the patients who took the test. Furthermore, use of esophagogastric monitoring makes it possible to identify the critical share of the non-acid reflux, i.e. mixed (21%) or alkaline (6%). Episodes of non-acid reflux feature a significantly higher rate of association with pain than acid reflux (12.5% of symptomatic acid refluxes, versus 6% of symptomatic acid refluxes, versus 6% of mixed refluxes and 7.15% of alkaline refluxes). Execution of an ergometric test, performed according to routine cardiologic procedures during pH monitoring, constitutes a valid stimulation for reflux-dependent pain, enabling us to achieve a diagnostic gain of 15.5% compared to pH monitoring alone. As stated, elicitation of pain by motor causes is performed using endo-esophageal distension (positive in 30% of cases) and with electrostimulation, a new test studied at our center.(ABSTRACT TRUNCATED AT 250 WORDS)