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.

Immunomodulatory properties of human recombinant lactoferrin in mice: Implications for therapeutic use in humans.

BACKGROUND: Trauma and major surgery cause extensive immune hyporeactivity in patients. Thus, the preventive, preoperative application of immunoregulatory therapeutics may normalize this immune reactivity and decrease morbidity and mortality in these subjects. OBJECTIVES: The aim of this study was to investigate the immunomodulatory actions of recombinant human lactoferrin (rhLF) in mice, and to relate these effects to in vitro actions of rhLF on tumor necrosis factor alpha (TNF-α) production in lipopolysaccharide-stimulated whole blood cell cultures (LPS-stimulated WBCC) from patients admitted to intensive care units. MATERIAL AND METHODS: BALB/c and CBA mice were used. rhLF was tested for allergic response to ovalbumin (OVA), delayed-type hypersensitivity (DTH) to OVA, and carrageenan-induced inflammation in an air pouch. Blood samples from 30 patients diagnosed with severe sepsis/septic shock (Apache II 21 ±1, mortality rate 40%) were collected on days 1, 3 and 5 of observation. The effects of rhLF on LPS-induced TNF-α production were measured in WBCCs. RESULTS: Recombinant human lactoferrin reduced the parameters of OVA-induced inflammation and inhibited the elicitation phase of DTH and carrageenan-induced inflammation in mice. The majority of patients from whom whole blood cell cultures (WBCC) were established showed a strong hyporeactivity to LPS upon admission. rhLF exerted differential effects on the production of LPS-induced TNF-α in those cultures on days 1, 3 and 5 of observation. Cytokine production was upregulated only in patients with sustained anergy to LPS, and inhibited or unchanged in moderately reactive patients. CONCLUSIONS: Evidence for the potential preventive or therapeutic utility of rhLF in patients with impaired immune reactivity has been demonstrated.

Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia-reperfusion model involving aortic clamping.

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia-reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)-sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.

Preoperative thromboelastometry for the prediction of increased chest tube output in cardiac surgery: A retrospective study.

Bleeding following cardiac surgery is a serious event with potentially life-threatening consequences. Preoperative recognition of coagulation abnormalities and detection of cardiopulmonary bypass (CPB) related coagulopathy could aid in the start of preventive treatment strategies that minimize perioperative blood loss. Most algorithms that analyze thromboelastometry coagulation tests in elective cardiac surgery do not include test results performed before surgery. We evaluated preoperative rotational thromboelastometry test results for their ability to predict blood loss during and after cardiac surgery.A total of 114 adult patients undergoing cardiac surgery with CPB were included in this retrospective analysis. Each patient had thromboelastometry tests done twice: preoperatively, before the induction of anesthesia and postoperatively, 10 minutes after heparin reversal with protamine after decannulation.Patients were placed into 1 of 2 groups depending on whether preoperative thromboelastometry parameters deviated from reference ranges: Group 1 [N = 29; extrinsically activated test (EXTEM) or INTEM results out of normal range] or Group 2 (N = 85; EXTEM and INTEM results within the normal range). We observed that the total amount of chest tube output was significantly greater in Group 1 than in Group 2 (700 mL vs 570 mL, P = .03). At the same time, the preoperative values of standard coagulation tests such as platelet count, aPTT, and INR did not indicate any abnormalities of coagulation.Preoperative coagulation abnormalities diagnosed with thromboelastometry can predict increased chest tube output in the early postoperative period in elective adult cardiac surgery. Monitoring of the coagulation system with thromboelastometry allows rapid diagnosis of coagulation abnormalities even before the start of the surgery. These abnormalities could not always be detected with routine coagulation tests.

Changes in the level of cardiac troponine and disorders in pulmonary gas exchange as predictors of short- and long-term outcomes of patients with aneurysm subarachnoid haemorrhage.

SUBJECT: Cardiopulmonary abnormalities are common after aneurysmal subarachnoid haemorrhage (aSAH). However, the relationship between short- and long-term outcome is poorly understood. In this paper, we present how cardiac troponine elevations (cTnI) and pulmonary disorders are associated with short- and long-term outcomes assessed by the Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOSE). METHODS: A total of 104 patients diagnosed with aSAH were analysed in the study. The non-parametric U Mann-Whitney test was used to evaluate the difference between good (GOS IV-V, GOSE V-VIII) and poor (GOS I-III, GOSE I-IV) outcomes in relation to cTnI elevation and pulmonary disorders. Outcome was assessed at discharge from the hospital, and then followed up 6 and 12 months later. Pulmonary disorders were determined by the PaO2/FiO2 ratio and radiography. The areas under the ROC curves (AUCs) were used to determine the predictive power of these factors. RESULTS: In the group with good short-term outcomes cTnI elevation on the second day after aSAH was significantly lower (p = .00007) than in patients with poor short-term outcomes. The same trend was observed after 6 months, although there were different results 12 months from the onset (p = .024 and n.s., respectively). A higher peak of cTnI was observed in the group with a pathological X-ray (p = .008) and pathological PaO2/FiO2 ratio (p ≪ .001). cTnI was an accurate predictor of short-term outcomes (AUC = 0.741, p ≪ .001) and the outcome after 6 months (AUC = 0.688, p = .015). CONCLUSION: The results showed that cardiopulmonary abnormalities perform well as predictive factors for short- and long-term outcomes after aSAH.

Comparison of anaesthetic gas consumption and stability of anaesthesia using automatic and manual control over the course of anaesthesia.

BACKGROUND: The automatic control module of end-tidal volatile agents (EtC) was designed to reduce the consumption of anaesthetic gases, increase the stability of general anaesthesia and reduce the need for adjustments in the settings of the anaesthesia machine. The aim of this study was to verify these hypotheses. METHODS: The course of general anaesthesia with the use of the EtC module was analysed for haemodynamic stability, depth of anaesthesia, end-expiratory concentration of anaesthetic, number of ventilator key presses, fentanyl supply, consumption of volatile agents and anaesthesia and operation times. These data were compared with the data obtained during general anaesthesia controlled manually and were processed with statistical tests. RESULTS: Seventy-four patients underwent general anaesthesia for scheduled operations. Group AUTO-ET (n = 35) was anaesthetized with EtC, and group MANUAL-ET (n = 39) was controlled manually. Both populations presented similar anaesthesia stability. No differences were noted in the time of anaesthesia, saturation up to MAC 1.0 or awakening. Data revealed no differences in mean EtAA or the fentanyl dose. The AUTO-ET group exhibited fewer key presses per minute, 0.0603 min⁻¹, whereas the MANUAL-ET exhibited a value of 0.0842 min⁻¹; P = 0.001. The automatic group consumed more anaesthetic and oxygen per minute (sevoflurane 0.1171 mL min⁻¹; IQR: 0.0503; oxygen 1.8286 mL min⁻¹, IQR: 1,3751) than MANUAL-ET (sevoflurane 0.0824 mL min⁻¹, IQR: 0.0305; oxygen 1,288 mL min⁻¹, IQR: 0,6517) (P = 0.0028 and P = 0.0171, respectively). CONCLUSION: Both methods are equally stable and safe for patients. The consumption of volatile agents was significantly increased in the AUTO-ET group. EtC considerably reduces the number of key presses.

Prolonged Cardiopulmonary Bypass is a Risk Factor for Intestinal Ischaemic Damage and Endotoxaemia.

BACKGROUND: Intestinal ischaemia-reperfusion, a frequent occurrence during cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. We hypothesised that ischaemia-reperfusion following prolonged CPB could increase intestinal permeability and thus, lead to endotoxin translocation from the intestine to the bloodstream. MATERIAL AND METHODS: Patients subjected to coronary artery bypass grafting with CPB were included: Group 1 (CPB ≥90minutes) or Group 2 (CPB <90minutes). Intestinal Fatty Acid Binding Protein (I-FABP), TNF alpha, IL6, IL8, and endotoxin levels were measured before the induction of general anaesthesia (T1), at 6 (T2), and 24hours (T3) after surgery. RESULTS: The low level of I-FABP at T1 increased for every patient in Group 1 at T2 (from 1015.5pg/mL to 2608.5pg/mL, p=0.02) and in Group 2 (from 1123.5pg/ml to 2284.0pg/ml, p<0.001). Furthermore, at T3, the I-FABP level was over three times higher in Group 1 than in Group 2 (2178pg/mL vs 615pg/mL; p<0.001). I-FABP correlated with CPB time (R=0.6, p<0.001) at T3. After surgery, endotoxins were elevated in 73% of patients in Group 1 and in 32% in Group 2 and correlated with CPB time (at T2, R=0.5, p=0.002; at T3, R=0.4, p=0.016). CONCLUSIONS: The duration of CPB is linked to the release of biomarkers that indicate ischaemic-reperfusion damage to the gastrointestinal mucosa and endotoxaemia. I-FABP assay may help to identify patients presenting with intestinal damage, who are at risk of bacterial translocation.

Unchanged plasma levels of the soluble urokinase plasminogen activator receptor in elective coronary artery bypass graft surgery patients and cardiopulmonary bypass use.

OBJECTIVE AND DESIGN: The soluble urokinase plasminogen activator receptor (suPAR) has been recently recognized as a potential biological marker of various disease states, but the impact of a major surgical intervention on the suPAR level has not yet been established. The aim of our study was to investigate if the induction of a systemic inflammatory reaction in response to cardiopulmonary bypass would be accompanied by an increase in the plasma suPAR level. METHODS AND SUBJECTS: Patients undergoing coronary artery bypass grafting under cardiopulmonary bypass (CPB) were added. Based on the baseline suPAR level, patients were divided into group 1 (suPAR within normal range) or group 2 (suPAR above range). Blood was collected before the induction of anesthesia and 6 and 24 hours after surgery. Plasma suPAR, IL-6, IL-8, TNF-α, troponin I, NT-proBNP, and NGAL were quantified to assess the impact of surgical trauma on these markers. RESULTS: The baseline suPAR level was within the normal range in 31 patients (3.3 ng/mL), and elevated in 29 (5.1 ng/mL) (p<0.001). Baseline mediators of systemic inflammatory reaction concentrations (IL-6, TNF-α, and IL-8) and organ injury indices (troponin I, NT-proBNP, and NGAL) were low and increased after surgery in all patients (p<0.05). The surgery did not cause significant changes in the suPAR level either at 6 or 24 hours after, however the difference between groups observed at baseline remained substantial during the postoperative period. CONCLUSIONS: There was no change in the suPAR level observed in patients subjected to elective cardiac coronary artery bypass surgery and CPB, despite activation of a systemic inflammatory reaction.

Surgical site infections, International Nosocomial Infection Control Consortium (INICC) report, data summary of 30 countries, 2005-2010.

OBJECTIVE: To report the results of a surveillance study on surgical site infections (SSIs) conducted by the International Nosocomial Infection Control Consortium (INICC). DESIGN: Cohort prospective multinational multicenter surveillance study. SETTING: Eighty-two hospitals of 66 cities in 30 countries (Argentina, Brazil, Colombia, Cuba, Dominican Republic, Egypt, Greece, India, Kosovo, Lebanon, Lithuania, Macedonia, Malaysia, Mexico, Morocco, Pakistan, Panama, Peru, Philippines, Poland, Salvador, Saudi Arabia, Serbia, Singapore, Slovakia, Sudan, Thailand, Turkey, Uruguay, and Vietnam) from 4 continents (America, Asia, Africa, and Europe). PATIENTS: Patients undergoing surgical procedures (SPs) from January 2005 to December 2010. METHODS: Data were gathered and recorded from patients hospitalized in INICC member hospitals by using the methods and definitions of the Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) for SSI. SPs were classified into 31 types according to International Classification of Diseases, Ninth Revision, criteria. RESULTS: We gathered data from 7,523 SSIs associated with 260,973 SPs. SSI rates were significantly higher for most SPs in INICC hospitals compared with CDC-NHSN data, including the rates of SSI after hip prosthesis (2.6% vs. 1.3%; relative risk [RR], 2.06 [95% confidence interval (CI), 1.8-2.4]; P < .001), coronary bypass with chest and donor incision (4.5% vs. 2.9%; RR, 1.52 [95% CI, 1.4-1.6]; [P < .001); abdominal hysterectomy (2.7% vs. 1.6%; RR, 1.66 [95% CI, 1.4-2.0]; P < .001); exploratory abdominal surgery (4.1% vs. 2.0%; RR, 2.05 [95% CI, 1.6-2.6]; P < .001); ventricular shunt, 12.9% vs. 5.6% (RR, 2.3 [95% CI, 1.9-2.6]; P < .001, and others. CONCLUSIONS: SSI rates were higher for most SPs in INICC hospitals compared with CDC-NHSN data.

Consent to eventual treatment in the intensive care unit expressed within the consent form for elective anaesthesia and surgery.

In contemporary clinical practice, the issue of requesting patient consent to perform therapeutic treatment plays an important role. The conscious consent of a patient as an expression of one's will greatly strengthens the legality of medical procedures performed by a physician, regardless of the medical field. However, obtaining consent to treatment in the intensive care unit (ICU) often poses enormous difficulties in daily clinical work, and has in recent decades been the cause of much dispute between doctors and lawyers. The correct interpretation of the provisions under the relevant laws determines the safety and comfort of the medical practice in the ICU. This study compared the current rules of normative acts of Polish common law relating to medical practice in intensive care units and issued on the basis of the judgments of the common court of law over the past ten years. On the basis of those provisions, the authors conclude that the patient should be informed by the anaesthesiologist during the visit as to the possibility of postoperative therapy in the ICU. The extent of such information depends on the likelihood of having treatment in the ICU. The consent of the patient for hospitalisation in the ICU should be mandatory in the case of treatments which are very likely to necessitate such hospitalisation. This concerns especially cardiac surgery, neurosurgery and treatments for patients with a significant burden of disease. The authors of this study propose that an information and consent form to undergo treatment in the intensive care unit should be included within the anaesthesia consent form.

[Leukemoid reaction with uncommonly high leucocytosis in the course of serious infection]. / Odczyn bialaczkowy z niespotykanie wysoka leuko- cytoza w przebiegu ciezkiego zakazenia.

We present a case of 51-year old female patient with gastrointestinal perforation and septic shock leading to leukemoid reaction with WBC 155 x 109/l. Leukemoid reaction in neoplasms and infections can mimic chronic myelogenous leukaemia and is an important diagnostic problem.