Changes in colloid solution sales in Nordic countries.

BACKGROUND: Administration of resuscitation fluid is a common intervention in the treatment of critically ill patients, but the right choice of fluid is still a matter of debate. Changes in medical practice are based on new evidence and guidelines as well as traditions and personal preferences. Official warnings against the use of hydroxyl-ethyl-starch (HES) solutions have been issued. Nordic guidelines have issued several strong recommendations favouring crystalloids over colloids in all patient groups. Our objective was to describe the patterns of colloid use in Nordic countries from 2012 to 2016. METHODS: The data were obtained from companies that provide pharmaceutical statistics in different countries. The data are sales figures from pharmaceutical companies to pharmacies and health institutions. RESULTS: We found a 56% reduction in the total sales of all colloids in Nordic countries over a 5-year period. These findings were mainly related to a 92% reduction in the sales of HES solutions. A reduction in sales of other synthetic colloids has also occurred. During the same period, we found a 46% increase in albumin sales, but these numbers varied between Nordic countries. CONCLUSION: The general reduction in colloid sales likely reflects the recommendation that colloids should be used only in special circumstances. The dramatic reduction in the sales of HES solutions was expected given evidence of harm and the official warnings. The steady increase in albumin sales and the notable differences between the five Nordic countries cannot be explained.

Claims for compensation after injuries related to airway management: a nationwide study covering 15 years.

BACKGROUND: Securing the airway is one of the most important responsibilities in anaesthesia. Injuries related to airway management can occur. Analysis from closed claims can help to identify patterns of injury, risk factors and areas for improvement. METHODS: All claims to The Norwegian System of Compensation to Patients from 1 January 2001 to 31 December 2015 within the medical specialty of anaesthesiology were studied. Data were extracted from this database for patients and coded by airway management procedures. RESULTS: Of 400 claims for injuries related to airway management, 359 were classified as 'non-severe' and 41 as 'severe'. Of the severe cases, 37% of injuries occurred during emergency procedures. Eighty-one claims resulted in compensation, and 319 were rejected. A total of €1,505,344 was paid to the claimants during the period. Claims of dental damage contributed to a numerically important, but financially modest, proportion of claims. More than half of the severe cases were caused by failed intubation or a misplaced endotracheal tube. CONCLUSION: Anaesthesia procedures are not without risk, and injuries can occur when securing the airway. The most common injury was dental trauma. Clear patterns of airway management that resulted in injuries are not apparent from our data, but 37% of severe cases were related to emergency procedures which suggest the need for additional vigilance. Guidelines for difficult intubation situations are well established, but adherence to such guidelines varies. Good planning of every general anaesthesia should involve consideration of possible airway problems and assessment of pre-existing poor dentition.

Tachyphylaxis to local anaesthetics. What is the clinical evidence? A systematic review.

BACKGROUND: Tachyphylaxis or acute tolerance to local anaesthetics has been reported, but the prevalence in clinical analgesia is obscure, and the mechanisms behind this phenomenon remain unclear. We sought to examine the clinical significance of tachyphylaxis from the available literature. METHODS: We performed a systematic review of the literature utilising the databases PubMed and Embase employing the search terms [Tachyphylaxis AND Local Anaesthetics AND Human] AND [Tolerance AND Local Anaesthetics AND Human]. RESULTS: A total of 66 records were identified. Thirty-four articles were assessed in full text for eligibility. Twenty studies were considered relevant for qualitative analyses, but only six studies were randomised controlled trials. Because of the heterogeneity of the randomised controlled trials, it was not possible to conduct a meta-analysis. CONCLUSION: Studies documenting tachyphylaxis with clinical use of local anaesthetics are surprisingly scarce, and the mechanisms behind it remain unclear.

Prevalence and predictors of persistent post-surgical pain 12 months after thoracotomy.

BACKGROUND: Persistent post-surgical pain is recognised as a major problem. Prevalence after different surgical procedures has been reported to range from 5% up to 85%. Limb amputation and thoracotomy have the highest reported prevalence. Prediction of persistent post-surgical pain has over the last decade caught attention. Several factors have been investigated, but in-depth knowledge is still scarce. The purpose of this study was to investigate the prevalence of persistent post-surgical pain, and predictive factors for persistent post-surgical pain 12 months after thoracotomy. METHODS: A prospective longitudinal study was conducted. One-hundred and seventy patients were recruited before scheduled thoracotomy, and asked to answer a questionnaire. One-hundred and six patients completed the same questionnaire at 12-month follow-up. Regression analysis was performed to explore variables assumed predictive of persistent post-surgical pain. RESULTS: One-hundred and six patients (62%) filled out the questionnaire at both time points. Preoperative, 34% reported muscle-skeletal related chronic pain. At 12-month follow-up, 50% of the patients reported persistent post-surgical pain. Of the variables explored in the logistic regression model, only preoperative pain (P < 0.001) and dispositional optimism (P = 0.04) were statistically significant. In this study, preoperative pain was a predominant predictor for persistent postoperative pain (OR 6.97, CI 2.40-20.21), while dispositional optimism (OR 0.36, CI 0.14-0.96) seem to have protective properties. CONCLUSION: Our results show that preoperative pain is a predominant predictor of future pain. This implies that patients presenting with a chronic pain condition prior to surgery should be assessed thoroughly preoperatively and have an individually tailored analgesic regimen.

Does chronic pre-operative pain predict severe post-operative pain after thoracotomy? A prospective longitudinal study.

BACKGROUND: Despite advances in pain research, many patients still experience moderate to severe post-operative pain that needs to be alleviated. The primary aim of this study was to identify predictive factors for severe post-operative pain after thoracotomy. Secondary, we investigated the levels of post-operative pain in this group of patients. METHODS: A prospective longitudinal study with 144 patients scheduled for thoracotomy was conducted between December 2007 and August 2010. All patients were given a questionnaire consisting of three sections (Brief Pain Inventory, Life Orientation Test-revised and Hospital Anxiety and Depression Scale) the day before surgery. Only those patients with pre-existing chronic pain were asked to complete all three sections. Post-operative pain scores were recorded three times a day for 6 days using the Numeric Rating Scale, and all analgesic consumption was recorded daily. RESULTS: Fifty-four patients reported pre-existing pain before surgery, most commonly from the neck, shoulders, lower back, hips or knees. For the first 3 days after surgery, the pain scores for those who had pre-existing chronic pain and those who did not, where almost similar with no statistically significant difference. The total amount of the epidural analgesia-mixture used where also almost similar for both groups with no statistically significant difference. CONCLUSION: In contrast to previous studies, which have reported pre-operative chronic pain to be a strong predictor of moderate to severe post-operative pain, we have in our study not been able to replicate these findings.

Infusions of albumin increase free fraction of naproxen in healthy volunteers: a randomized crossover study.

BACKGROUND: In vitro and in vivo studies have indicated that stabilizers present in pharmaceutical-grade albumin influence the albumin-binding capacity for highly protein-bound drugs. However, the half-life of the stabilizers and the quantitative effect have been difficult to determine. METHOD: A randomized crossover study including six healthy volunteers was performed. The study subjects received 750 mg of oral naproxen 2 h before the study. They were randomized to receive either 100 ml of 20% albumin or 100 ml of Ringer's acetate solution intravenously. Frequent blood samples were obtained. The experiment was repeated 4 weeks later with the alternate solution. The serum samples were analysed to determine the concentrations of albumin, N-acetyl-DL-tryptophan, caprylate, and naproxen. RESULTS: The free fraction of naproxen increased significantly after the infusion of albumin (P<0.05). The increase was concurrent with the appearance of N-acetyl-DL-tryptophan and caprylate in serum. The free fraction of naproxen declined rapidly after the albumin infusion was completed. N-acetyl-DL-tryptophan had a half-life of approximately 30 min. The half-life of caprylate was <15 min. CONCLUSION: A transfusion of albumin results in an increase in the free fraction of naproxen. The transient increase in free-fraction naproxen decreased together with the detectable levels of the stabilizers N-acetyl-DL-tryptophan and caprylate. N-acetyl-DL-tryptophan and caprylate have a short half-life in serum.

Hyperbaric oxygen therapy for late radiation tissue injury in gynaecological patients.

BACKGROUND: Pelvic radiation therapy is an important element of curative therapy for gynaecological cancers. Serious radiation-related complications developing months or years after treatment are known as late radiation tissue injury (LRTI). METHODS: We investigated the possible pain reducing effect of hyperbaric oxygen treatment (HBOT) in a study of 16 patients with LRTI after radiation for gynaecological malignancy. The 16 patients were registered prospectively, underwent HBOT for 21 consecutive days and were followed for a 6-month period after treatment using the Brief Pain Inventory, Montgomery and Aasberg Depression Rating Scale, as well as registration of global patient scores, analgesic consumption and magnetic resonance imaging (MRI) findings. RESULTS: HBOT was shown to have insignificant effect on pain, pain characteristics, daily function, the use of analgesics and MRI-related tissue injury. Fifty percent of the patients still reported some or good effect of the treatment. CONCLUSION: It is not possible to conclude from our study if gynaecological patients with pelvic pain will benefit from HBOT. The application of HBOT to selected patients may be justified, but further research with adequate sample size, as well as the timing of HBOT related to the development of LRTI, is required to establish the optimum patient selection.

Infusion of albumin attenuates changes in serum protein binding of drugs in surgical patients compared with volume replacement with HAES.

BACKGROUND: In vitro studies have indicated that stabilizers present in pharmaceutical-grade albumin influence albumin-binding capacity for highly protein bound drugs. METHODS: A randomized study including 40 surgical patients, treated with either albumin or starch solutions, was performed. Volumes of colloids were given based on clinical indication. Blood samples were obtained. The serum samples were analyzed to determine the concentrations of albumin, tryptophan, N-acetyl-dl-tryptophan, caprylate and alpha-1-acid glycoprotein as well as in vitro drug binding of naproxen, warfarin and digitoxin. RESULTS: During surgery, the albumin concentration declined in the Starch group from 26.8 to 15.3 g/l. It remained unchanged in the Albumin group (29.2 g/l). The two groups were analyzed with the pre-operative sample acting as the control. In the starch group, the percent free concentration of the drugs increased significantly (P<0.01): for naproxen from 0.2% to 0.6%, for warfarin from 1.2% to 1.8% and for digitoxin from 6.8% to 11.1%. In the Albumin group, the % free fraction of naproxen doubled from 0.1% to 0.2% (P<0.05), whereas the % free fraction of warfarin decreased from 1.1% to 1.0% (P<0.05). The free fraction of digitoxin remained unchanged. CONCLUSIONS: Infusion of albumin during surgery resulted in maintained albumin values and almost maintained binding parameters for the study drugs, although some statistically significant changes were found. The use of starch solutions, however, led to in a reduction in albumin values and a significant reduction in binding parameters.

Mechanical ventilation in critically ill cancer patients: outcome and utilisation of resources.

Intensive care is increasingly being used in the management of cancer patients. It is important that a disproportionate share of special care resources is not expended on futile care of terminally ill patients. A requirement for mechanical ventilation has been stated to affect survival in cancer patients. The objectives of this study were to determine our hospital utilisation of ICU facilities and the prospects of a successful outcome in cancer patients with a need for ventilatory support. The Norwegian Radium Hospital is a 400-bed cancer hospital with a 12-bed combined postoperative and intensive care unit (PO/ICU). For each patient admitted to the PO/ICU, patient data including diagnosis, therapeutic interventions, use of resources and outcome are entered in a computerised database. We reviewed all 10,051 patients admitted during a 5-year period, focusing on the patients receiving ventilatory support. There were 347 patients who were treated with mechanical ventilation, 228 patients only for a short period postoperatively after extensive surgery. A further 119 patients (mean age 68 years, mean SAPS 33.5) were treated with mechanical ventilation for more than 24 h or died during treatment in the ICU; 65 patients (55%) were admitted after elective surgery, 24 (20%) after surgical emergencies and 30 (25%) after medical emergencies. Metastatic disease was present in 59% of them. These 119 patients comprised 1.18% of all patients admitted to the PO/ICU, but utilised 28% of all resources. They included 34 patients (29%) who died during the ICU stay, while 69 patients (58%) were still alive after 6 months. The ICU mortality in different groups was: surgical patients 24%, gynaecological patients 9%, oncological patients 63%. The mortality in the age group >70 years was 15%. The role of ICU facilities, including mechanical ventilation, is important for optimal supportive care in cancer patients. Our results indicate that this treatment modality should not generally be restricted in critically ill cancer patients. The quality of life of the patients who survived should be of interest to those involved in further medical and ethical decisions concerning the level of care in the ICU.

[Accepted low hemoglobin levels in the perioperative period. A questionnaire survey among Norwegian anesthesiologists]. / Aksepterte nedre hemoglobingrenser i den perioperative periode. En spørreundersøkelse blant norske anestesileger.

Declining haemoglobin concentrations are accepted in order to avoid allogeneic blood transfusions in surgical patients. A questionnaire was sent to all members of the Norwegian Association of Anaesthesiologists addressing the question of safe blood levels of haemoglobin in different patient groups, and the different blood conservation techniques used in their hospital. 206 questionnaires (49%) were returned. Intraoperative and postoperative autotransfusions were the two most frequently used methods of saving blood. The survey demonstrates a wide diversity in the accepted lower haemoglobin levels, especially in children, and in spite of its limitations sheds light on Norwegian anaesthetists' routines as regards the indications for blood transfusion and blood conservation in the perioperative period.

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. METHODS: This study evaluated the efficacy of a blood transfusion filter in removing tumour cells from blood. Whole human blood was admixed with two different malignant cell lines (breast cancer PM1 and MCF7). The blood was filtered through a RC400TE leucocyte depletion filter. Unfiltered blood was used as a control. Detection of malignant cells was performed with immunomagnetic beads and clonogenic assays. RESULTS: No viable tumour cells were found after filtration with the leucocyte depletion filter. CONCLUSION: These findings suggest that the use of a leucocyte filter after intra-operative blood salvage may make autotransfusion safe even in tumour surgery.

Autotransfusion after open heart surgery: quality of shed mediastinal blood compared to banked blood.

The need to conserve a patient's own blood and avoid homologous transfusion is now well recognized. Therefore, techniques designed to reduce requirements for homologous blood transfusions have been developed. One of the methods is autotransfusion of shed mediastinal blood after open-heart surgery. The objectives of the present study were to investigate osmotic fragility and oxygen transport capacity of shed mediastinal blood compared to patient blood and stored packed red blood cells (SAGM). Shed mediastinal blood from ten consecutive patients undergoing elective cardiac surgery (coronary bypass grafting) was studied and compared to patient blood, 10 units of 3 weeks old and 10 units of 5 weeks old stored packed red blood cells (SAGM). Oxygen transport capacity was investigated by calculation of p50 for oxygen by use of the oxygen status algorithm (OSA 2.0) programme and measurement of 2,3-diphosphoglycerate (2,3-DPG) concentrations. The osmotic fragility was determined using increasing concentrations of saline. 2,3-DPG concentrations in shed mediastinal blood (5.3 mikromol/ml erythrocyte) were within the range measured in patient blood, but significantly higher than SAGM blood (P < 0.001). P50 for oxygen (3.5 kPa) in shed mediastinal blood was not significantly different compared to patient blood, but significantly higher (P < 0.01) compared with stored SAGM blood. The osmotic fragility in shed mediastinal blood was not significantly different compared to patient blood, but significantly lower (P < 0.001) than the osmotic fragility in stored SAGM blood. This suggests that red cells saved from shed mediastinal blood have better oxygen transport capacity and may have longer survival compared to stored blood.

[Infusion of barbiturates as a compenent in the treatment of refractory pain in patients with terminal cancer]. / Barbituratinfusjon som ledd i behandling av refraktaere smerter hos kreftpasienter i terminalfasen.

Four patients with advanced cancer were referred to the Pain Team because of refractory pain symptoms. They received intravenous barbiturates prior to death. All attempts at palliative treatment had been exhausted. The symptoms were described by patients and family as unendurable. After adding intravenous thiopental, relief and tranquility were achieved. All four patients died peacefully. The need to sedate to a state of unconsciousness or semi-consciousness to relieve symptoms in dying cancer patients is extremely rare. After all viable alternatives have been explored, titrated barbiturate infusion as an adjuvant may fill a void in the care of especially challenging patients as they approach death from terminal cancer.

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 Ringer-Dextran 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.

Platelets in shed mediastinal blood used for postoperative autotransfusion.

Ten patients undergoing open-heart surgery received postoperative autotransfusion of shed mediastinal blood collected in the cardiotomy reservoir. The number, function and morphology of the platelets found in the shed blood were investigated. Platelets were counted using an electronic counter compared with light microscopy. Morphology of platelets was studied with electron microscopy. Platelet aggregation was studied using an aggregometer. Dense granule secretion was measured as the extracellular appearance of adenosine triphosphate. Enumeration of platelets in shed blood using the two methods gave different results. Thus, the electronic counter gave a mean platelet count of 62 x 10(9).l-1, while light microscopy revealed only a mean platelet count of 10 x 10(9).l-1. Electron microscopy disclosed few platelets, but numerous cytoplasmatic fragments smaller than or up to the same size as platelets. The platelets found were mostly shape-changed, spheroid, characterized by centralization and loss of alpha-granules and dense bodies, all changes that indicated irreversible platelet activation. The platelets failed to aggregate in response to the presence of thrombin, adenosine diphosphate or collagen, and secretion of adenosine triphosphate was absent. Plasma from the shed blood was not capable of inducing spontaneous aggregation in platelet-rich plasma from healthy donors. These results indicate that infusion of larger volumes of autotransfused blood should be supplemented with platelet concentrates.

[Capnography. A new monitoring method may improve patient safety during anesthesia and in the recovery room]. / Kapnografi. Ny monitorering som kan bedre pasientsikkerheten ved anestesi og i overvåkingsavdeling.

This review describes the diagnostic possibilities of capnography: the graphic presentation of carbon dioxide concentrations in respiratory gas during the entire respiratory cyclus. The monitoring may confirm that the tube used for intubating the patient's trachea is positioned in the patient's airway, and indicates dysfunction of the tube or of the ventilator. Capnography can also rapidly provide important information about a patient's ventilation, circulation and metabolism. This may improve patient safety during anaesthesia and in the intensive care unit. Patients without artificial airways may also be monitored by capnography. The method may reduce the number of arterial blood gases required to check the degree of ventilation.

Effects of heparin on proteolytic activities in human plasma.

The influence of unfractionated heparin [average molecular weight (MW) 10,000-15,000 kD] and low-molecular-weight heparin (average MW 400-600 kD) on the plasma kallikrein-kinin and the fibrinolytic system was studied in vitro. Unfractionated heparin added to plasma gave an increase in kallikrein-like activity with a corresponding decrease of prekallikrein and functional kallikrein inhibition values. Plasmin-like activity was also increased, but minor changes in plasminogen and no change in antiplasmin values occurred. The changes were less pronounced with low molecular heparin compared with unfractionated heparin. The proteolytic changes were reversed by protamine sulfate but not influenced by the protease inhibitor aprotinin. Gel filtration yielded proteolytic activities able to split the plasma kallikrein substrate S-2305 and, to a minor degree, the plasmin substrate S-2251. The proteolytic activities were not due to complex formation with alpha 2-macroglobulin. We speculate that heparin binds to prekallikrein to form a heparin-prekallikrein complex which undergoes conformational changes and displays a kallikrein-like activity with the ability to split small synthetic substrates. Whether it is capable to split natural substrates remains unresolved.

Haemodynamic effects of heparin during coronary bypass surgery.

Heparin has been suggested as an activator of the plasma kallikrein-kinin system, with possible formation of bradykinin, a potent vasodilator. Haemodynamic effects and changes in the kallikrein-kinin system were studied after heparin- and saline-injections in ten patients undergoing coronary bypass surgery. A moderate decrease in mean arterial pressure was found in all patients in the observation period, but significantly more at 2 and 3 min after heparin-injection compared with saline-injection. None of the other haemodynamic variables measured were significantly different when comparing heparin- to saline-injection. Heparin-injection resulted in significant changes in the kallikrein-kinin system, with a marked increase in spontaneous kallikrein-like activity as the most prominent feature, while no changes were found after saline-injection. Liberation of bradykinin would be expected to give a decrease in systemic vascular resistance with an increase in cardiac output. The results indicate that the plasma kallikrein-kinin system, though apparently activated after heparin-injection, does not contribute significantly to the decrease in arterial pressure in the patients studied.

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. Hematologic 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/l, a platelet count of 71 and 119 x 10(9)/l, and plasma haemoglobin level of 3110 and 4100 mg/l 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/l to 430 mg/l. The clinical safety and simplicity of this technique were confirmed for autotransfusion of shed mediastinal blood up to 1200 ml.