Ulf E. Kongsgaard

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non‐malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non‐malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro‐fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non‐malignant pain.

Prevalence of pain in hospitalised cancer patients in Norway: a national survey.

Purpose: Pain severely impairs health-related quality of life and is a feared symptom among cancer patients. Unfortunately, patients often do not receive optimal care. We wanted to evaluate the quality of cancer pain treatment in Norwegian hospitals. Patients and methods: A one-day prevalence study targeting hospitalised cancer patients above 18 years of age was performed. A questionnaire based on the Brief Pain Inventory was used, and additional information regarding sex, age, diagnosis, break through pain (BTP), and treatment was included. Results: Fifty two percent of the included patients stated having cancer related pain (n = 453), and mean pain during the previous 24 hours for these patients was NRS 3.99 (Numeric Rating scale 1-10). Presence of metastasis, occurrence of BTP, and abnormal skin sensibility in the area of pain were associated with higher pain scores. Forty two percent of all patients used opioids. However, these patients still had higher pain scores, more episodes of BTP, and more influence of the pain on daily life functions than average. Thirty percent of patients with severe pain (NRS ≥ 5) did not use opioids, and some of these patients did not receive any analgesics at all. Conclusion: Although most cancer patients receive an acceptable pain treatment in Norwegian hospitals, there are patients who are not adequately managed. Lack of basic knowledge and individual systematic symptom assessment may be reasons for the underuse of analgesics and the resulting unnecessary suffering among the cancer patients.

Fluid balance and pulmonary functions during and after coronary artery bypass surgery: Ringer's acetate compared with dextran, polygeline, or albumin

The effects on fluid balance, pulmonary tunctions and economics were evaluated in a randomized comparison of one colloid free and three colloid containing fluid regimens, for 48 hours during and after coronary artery‐bypass (CAB) surgery.

Colloid osmotic pressure of plasma replacement fluids

Colloid osmotic pressure (COP) of some of the most frequently used plasma replacement fluids was measured with a colloid osmometer. COP of 4% human albumin solutions was only half that of normal human serum (13.6±0.6 vs. 27.5 ± 2.7 mmHg (1.8±0.1 vs. 3.7±0.4 kPa)) (mean±s.d.), whereas COP of 20% human albumin solutions was eight times higher (196.0±12.3 mmHg (26.1 ± 1.6 kPa)). Enhancing the protein concentration from 4% to 20% in the human albumin solutions increased COP 14‐fold, reflecting the exponential relationship between protein concentration and COP of a solution. Fresh donor plasma furnished by the hospital blood‐bank had a COP about 30% below normal human serum (18.1 ± 1.3 mmHg (2.4 ± 0.2 kPa)), due to dilution during preparation. Dextran 70 (6%) had a COP more than twice, and RingerDextran 60 (3%) about 75% of that of normal human serum. Dextran 40 (10%) and gelatin (3.5%, Haemaccel) leaked markedly through the membrane of the colloid osmometer, making acceptable measurements impossible. Seven different hydroxyethyl starch (HES) solutions were measured, and the COP varied between half and 3 times that of normal human serum, depending on molecular weight and concentration of the HES.

Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro

BackgroundAlbumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company.MethodsThe binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism.ResultsThe drugs were highly bound to albumin (95–99.5%). The highest affinity (lowest K1) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilisers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilisers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity.ConclusionThis in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen no longer detectable in pharmaceutical-grade albumin. It further shows that the addition of stabilisers may be of major importance for this effect.

Leucocyte depletion filter removes cancer cells in human blood

Background. Autologous blood transfusion has been avoided in cancer surgery because of the metastatic potential of reinfused tumour cells.

Autotransfusion after open heart surgery: characteristics of shed mediastinal blood and its influence on the plasma proteases in circulating blood

Fourteen patients undergoing open‐heart surgery received intermittent or continuous postoperative autotransfusion of shed mediastinal blood (minimum 400 ml during 6 h after surgery) collected in the cardiotomy reservoir. Haemotologic variables and changes in the coagulation, fibrinolytic and plasma kallikrein‐kinin systems were investigated in the reservoir blood at the beginning and after 6 h of autotransfusion, and in patient blood during and after surgery and before and after autotransfusion. Autotransfusion volume ranged from 400 to 1200 ml per patient (median 482 ml). The reservoir blood had a median haemoglobin level of 93 and 74 g/1, a platelet count of 71 and 119times 109/1, and plasma haemoglobin level of 3110 and 4100 mg/1 before and after 6 h of autotransfusion, respectively: Further examination of the reservoir blood showed that it had undergone extensive coagulation and fibrinolysis as well as a moderate activation of the kallikrein‐kinin system. Despite these extensive alterations in the reservoir blood, no major change could be found in the circulating blood after autotransfusion, except for a moderate increase in plasma haemoglobin from 180 mg/1 to 430 mg/1. The clinical safety and simplicity of this technique were confirmed for autotransfusion of shed mediastinal blood up to 1200 ml.

Experience of unpleasant sensations in the mouth after injection of saline from prefilled syringes

BackgroundNurses at The Norwegian Radium Hospital have reported that some patients notice an unpleasant smell or taste in accordance with flushing of intravenous lines with commercially available prefilled syringes. We have conducted a study in healthy volunteers to investigate the occurrence, consistency and intensity of this phenomenon.MethodsA randomised, blinded, crossover study comparing commercial available prefilled saline 9 mg/ml syringes to saline 9 mg/ml for injection in polyethylene package was performed in 10 healthy volunteers. The volunteers were given intravenous injections of varying volume and speed. Data were analysed using descriptive statistics, and also Wilcoxon Signed Rank Test to compare groups.ResultsAfter intravenous injection, 2 of 15 recordings demonstrated any sensation of smell or taste after injection of saline from polyethylene package, while 14 of 15 recordings noted a sensation after injection of saline from prefilled syringes. The intensity of the unpleasant sensation was rated significantly higher after injection of saline from prefilled syringes compared to saline from polyethylene (p = 0.001).ConclusionsInjection of saline from prefilled syringes in healthy volunteers resulted in an experience of bad taste or smell. It is important that nurses and health workers are aware of the phenomenon as described in this article in order to choose the preferred product for a given patient.

Definition, diagnosis and treatment strategies for opioid-induced bowel dysfunction—Recommendations of the Nordic Working Group

Abstract Background and aims Opioid-induced bowel dysfunction (OIBD) is an increasing problem due to the common use of opioids for pain worldwide. It manifests with different symptoms, such as dry mouth, gastro-oesophageal reflux, vomiting, bloating, abdominal pain, anorexia, hard stools, constipation and incomplete evacuation. Opioid-induced constipation (OIC) is one of its many symptoms and probably the most prevalent. The current review describes the pathophysiology, clinical implications and treatment of OIBD. Methods The Nordic Working Group was formed to provide input for Scandinavian specialists in multiple, relevant areas. Seven main topics with associated statements were defined. The working plan provided a structured format for systematic reviews and included instructions on how to evaluate the level of evidence according to the GRADE guidelines. The quality of evidence supporting the different statements was rated as high, moderate or low. At a second meeting, the group discussed and voted on each section with recommendations (weak and strong) for the statements. Results The literature review supported the fact that opioid receptors are expressed throughout the gastrointestinal tract. When blocked by exogenous opioids, there are changes in motility, secretion and absorption of fluids, and sphincter function that are reflected in clinical symptoms. The group supported a recent consensus statement for OIC, which takes into account the change in bowel habits for at least one week rather than focusing on the frequency of bowel movements. Many patients with pain receive opioid therapy and concomitant constipation is associated with increased morbidity and utilization of healthcare resources. Opioid treatment for acute postoperative pain will prolong the postoperative ileus and should also be considered in this context. There are no available tools to assess OIBD, but many rating scales have been developed to assess constipation, and a few specifically address OIC. A clinical treatment strategy for OIBD/OIC was proposed and presented in a flowchart. First-line treatment of OIC is conventional laxatives, lifestyle changes, tapering the opioid dosage and alternative analgesics. Whilst opioid rotation may also improve symptoms, these remain unalleviated in a substantial proportion of patients. Should conventional treatment fail, mechanism-based treatment with opioid antagonists should be considered, and they show advantages over laxatives. It should not be overlooked that many reasons for constipation other than OIBD exist, which should be taken into consideration in the individual patient. Conclusion and implications It is the belief of this Nordic Working Group that increased awareness of adverse effects and OIBD, particularly OIC, will lead to better pain treatment in patients on opioid therapy. Subsequently, optimised therapy will improve quality of life and, from a socio-economic perspective, may also reduce costs associated with hospitalisation, sick leave and early retirement in these patients.

Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on haemodynamic parameters, transcapillary fluid balance, diuresis and atrial peptides.

The effects of Ringers acetate (RAc) infusion with different temperatures, 18d̀C compared to 36d̀C, were studied in 20 healthy volunteers. An infusion volume of 20% of the estimated extracellular volume was given over 45 min. Before and after the RAc infusion, interstitial colloid osmotic pressure and interstitial fluid hydrostatic pressure were measured on the lateral part of the thorax and in the lower leg. Blood sampling and pressure measurements were performed through a cannula placed in the left radial artery, and arterial oxygen saturation was measured by pulse oximetry. Atrial peptides ANF (99–126) and ANF (1–98) in plasma were measured as indicators of volume loading. Cold RAc infusion increased mean arterial pressure from 82 (s.d. ± 7) to 96 (s.d. ± 9) mmHg (10.9–12.8 kPa) at the end of the infusion with a simultaneous fall in heart rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The arterial oxygen saturation during the infusion of cold RAc was higher than during warm RAc infusion. Cold infusion produced the expected haemodilution with a fall in erythrocyte volume fraction (EVF) from 0.39 (± 0.03) to 0.33 (± 0.03) and a fall in plasma colloid osmotic pressure (COPp) from 21.7 (± 1.1) mmHg to 15.0 (± 1.3) mmHg (2.9–2.0 kPa). Warm infusion induced a nearly identical haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (± 2.3) mmHg to 8.9 (± 2.7) mmHg (1.5–1.2 kPa) after warm infusion while cold infusion gave no changes. The changes in interstitial fluid hydrostatic pressure were not significant. Cold infusion induced a higher diuresis compared to warm RAc infusion. ANF increased during cold, but not during warm infusion. We conclude that infusions of RAc at 18d̀C vs. 36d̀C have different volume effects. Cold infusion increased blood pressure and diuresis, while warm infusion induced peripheral vasodilation with increased capillary leakage and subcutaneous oedema formation.