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

BACKGROUND: Albumin 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. METHODS: The 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. RESULTS: The drugs were highly bound to albumin (95–99.5%). The highest affinity (lowest K(1)) 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. CONCLUSION: This 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

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

Background Nurses 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. Methods A 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. Results After 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). Conclusions Injection 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

Dynamic assessment of the pupillary reflex in patients on high-dose opioids

Background and aims Pupil size and reaction are influenced by opioids, an effect that is not considered to be affected by opioid tolerance. As clinicians have observed patients on high-dose opioids who exhibited seemingly normal pupil sizes, we wanted to dynamically assess the pupillary reflex in cancer patients on high-dose opioids. Methods We performed a dynamic assessment of the pupillary reflex in cancer patients on high-dose opioids and a control group of healthy volunteers using a portable, monocular, infrared pupillometer. We also performed a clinical examination and measured blood concentrations of opioids and their active metabolites. Results Sixty three patients who were on opioids for 2 months (median time) and on an oral morphine equivalent dose of 250 mg (median dose) were investigated. Most patients used more than one opioid. When correcting for age, pupil size in the group that had received no increase of opioid dose over the last 14 days was not significantly different from pupil size in the healthy volunteer group (p = 0.76), while the group that had increased the dose of opioids differed significantly from healthy volunteers (p = 0.006). We found no statistically significant correlation between total oral morphine equivalents and pupillary reactions or between blood opioid or opioid metabolite concentrations and baseline pupillary changes. Conclusion Pupillary changes do take place in patients on opioids. However, tolerance to these changes occurs when medication is not increased over time. Dynamic pupillometry can give additional information about the degree of tolerance to opioids. Implications These findings elucidate previous misconceptions regarding pupillary effects and tolerance to opioids

A patient with solid gynecologic cancer causing lactic acidosis, severe hypercalcemia, and hypoglycemia

publishedVersio

Potentially Severe Incidents During Interhospital Transport of Critically Ill Patients, Frequently Occurring But Rarely Reported: A Prospective Study

Objectives The out-of-hospital environment can pose significant challenges to the quality and safety of interhospital transport of critically ill patients. Because we lack knowledge of the occurrence of incidents, their potential consequences, and whether they are actually reported, this study was initiated. Methods Two different services in Norway were asked to self-report incidents after every interhospital transport of critically ill patients. Sampling lasted for 12 and 8 months, respectively. An expert group evaluated each incident for severity and demand for reporting into the hospital’s electronic incident reporting system. One year later, the hospital’s reporting system was scrutinized to determine the number of incidents actually reported. Results A total of 455 transports of critically ill patients were performed, resulting in 294 unique incidents reported: medical (15%), technical (25%), missing equipment (17%), and personal failures and communication difficulties (42%). Only 3 (1%) of the 294 unique incidents were actually reported in the hospital’s electronic incident reporting system. The experts were inconsistent in which incidents should have been reported and to what degree checklists, standard operating procedures, simulation, and training could have prevented the incidents. Conclusions This study of interhospital transports of critically ill patients reveals a very high number of incidents. Despite this fact, these incidents are severely underreported in the hospital’s electronic incident reporting system. This suggests that learning is lost and errors with predominant probability are repeated. These results emphasize the existing challenges in regard to the quality and safety of interhospital transport of critically ill patients

The effect of tracheotomy on drug consumption in patients with acute aneurysmal subarachnoid hemorrhage: an observational study

Background Patients with aneurysmal subarachnoid hemorrhage (aSAH) are common in intensive care units (ICU). In patients with aSAH, sedation is used as a neuroprotective measure in order to secure adequate cerebral perfusion pressure (CPP). Compared with the use of an endotracheal tube, a tracheotomy has the advantage of securing the airway at a much lower level of distress, and aSAH patients can often be awakened more rapidly. Little is known about the impact of tracheotomy on the consumption of sedative/analgesic and vasoactive drugs and the maintenance of CPP within defined limits in aSAH patients. Methods We conducted an observational study of aSAH patients who underwent percutaneous tracheotomy. A prospective registry of patient data was supplemented with retrospective retrievals from medical records. Sedative, analgesic and vasoactive drug doses were registered for 3 days prior to and after percutaneous tracheotomy, respectively. Blood pressure, CPP, and the mode of mechanical ventilation were registered 24 h prior to and after tracheotomy. Results Between January 2001 and June 2009, 902 aSAH patients were admitted to our hospital; 74 (8%) were deeply comatose/dying upon arrival. The ruptured aneurysm was repaired in 828 patients (surgical repair 50%) and percutaneous tracheotomy was performed 182 times in 178 patients (59 men and 119 women). This subpopulation (178 of 828 patients) was significantly older (56 vs. 53 years) and presented with a more severe Hunt & Hess grade (p < 0.001). Percutaneous tracheotomy caused a marked decline in mean daily consumption of the analgesics/sedatives fentanyl, midazolam, and propofol, as well as the vasoactive drugs noradrenaline and dopamine. These declines were statistically and clinically significant. The mean CPP was 76 mmHg (SD 8.6) the day before and 79 mmHg (SD 9.6) 24 h after percutaneous tracheotomy. After percutaneous tracheotomy, mechanical ventilatory support could be reduced to a patient-controlled ventilatory support mode in a significant number of patients (p < 0.001). Conclusions Percutaneous tracheotomy in aSAH patients is a swift procedure with low risk that is associated with a significant decline in the consumption of sedative/analgesic and vasoactive drugs while clinical surveillance parameters remain stable or improve

Interhospital transport of critically ill patients: experiences and challenges, a qualitative study

Background No consensus based national standard for interhospital transports of critically ill patients exists in Norway. The local hospitals are responsible for funding, organizing and performing these transports, resulting in potentially different level of care for the critically ill patients depending on local hospital resources and not the level of severity in the patient’s condition. The aim of this study was to examine how these transports are executed and to discover challenges during transports and potentials of improvement. Methods A qualitative study with 20 semi-structured interviews of doctors, nurses and ambulance personnel representing a wide range in experience and formal education, reflecting the different compositions of crews performing interhospital transports was conducted. A systematic text condensation of the interviews was performed to describe personal experiences and values. Results Few interviewees reported special adverse events when asked. Instead they chose to describe more general characteristics of the working environment, their own positive emotions or fears and the strengths and weaknesses of the organizational system. The prehospital working environment was described as different from the in-hospital environment. The personnel experienced being on their own during transports, lack of procedures and checklists and often no systematic education or demanded preparedness for participating. The resident doctors described pressure from elderly colleagues to participate in the transports. At the same time, all interviewees reported a self-interest in participating in these transports. Conclusions Safe interhospital transports of the critically ill patients are challenged by the characteristics of the out of hospital environment. The transports are described as potentially unsafe for both patients and personnel. Systematic education is warranted, highlighting the use of checklists and special educational programs in prehospital critical care medicine. The strong personal interest to participate in these transports may serve as a barrier against changing todays system. To ensure the right level of competence and safety for each unique patient, it is imperative to standardize the interhospital transports on a national level, built on consensus from experienced prehospital personnel. Trial registration The trial is approved and registered by the local representative for the Norwegian Data Protection Authority as trial 13–7751

Post-thoracotomy pain syndrome and sensory disturbances following thoracotomy at 6-and 12-month follow-ups

Background: Persistent pain affects a large proportion of patients after thoracotomy and is associated with sensory disturbances. The objective of this prospective study was to investigate the time course of pain and sensory disturbances over a 12-month period. Methods: Patients scheduled for thoracotomy were recruited. Data were collected on the day before surgery, including baseline characteristics and the presence of any preoperative pain. At 6- and 12-month follow-ups, data on pain were collected using the Brief Pain Inventory-Short Form, and perceived sensory disturbances around the thoracotomy scar were recorded from a self-exploration test. Results: At 12 months after surgery, 97 patients had complete data including baseline and 6- and 12-month measurements. Almost half of the patients reported post-thoracotomy pain at the follow-ups. However, 20% of the patients not reporting post-thoracotomy pain at 6 months did report it at 12 months. Between 40% and 60% of patients experienced some kind of sensory disturbance at 6 months. A small decline in some kind of sensory disturbance was reported by 20%–50% of patients at 12 months. Conclusion: A proportion of patients experienced either resolved or delayed onset of pain. Sensory changes were strongly associated with post-thoracotomy pain syndrome, but were also present in a large proportion of patients without it