Folke Sjöberg

Measurement of depth of burns by laser Doppler perfusion imaging

Laser Doppler perfusion imaging (LDPI), is a further development in laser Doppler flowmetry (LDF). Its advantage is that it enables assessment of microvascular blood flow in a predefined skin area rather than, as for LDF, in one place. In many ways this method seems to be more promising than LDF in the assessment of burn wounds. However, several methodological issues that are inherent in the LDPI technique, and are relevant for the assessment of burn depth, must be clarified. These include the effect of scanning distance, curvature of the tissue, thickness of topical wound dressings, and pathophysiological effects of skin colour, blisters, and wound fluids. Furthermore, we soon realised that to examine the perfusion image generated by LDPI adequately the process of analysis was appreciably improved by the simultaneous use of digital photography. In the present investigation we used both in vitro and in vivo models and also examined burned patients, and found that the listed factors all significantly affected the LDPI output signal. However, if these factors are known to the examiner, most of them can be adjusted for. If the technique is further improved by minimizing such effects and by reducing the practical difficulties of applying it to a burned patient in the burns unit, the technique may find uses in everyday clinical decision-making.

The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans

Atherosclerotic cardiovascular disease is a major problem despite the availability of drugs that influence major risk factors. New treatments are needed, and there is growing interest in therapies that may have multiple actions. Thyroid hormone modulates several cardiovascular risk factors and delays atherosclerosis progression in humans. However, use of thyroid hormone is limited by side effects, especially in the heart. To overcome this limitation, pharmacologically selective thyromimetics that mimic metabolic effects of thyroid hormone and bypass side effects are under development. In animal models, such thyromimetics have been shown to stimulate cholesterol elimination through LDL and HDL pathways and decrease body weight without eliciting side effects. We report here studies on a selective thyromimetic [KB2115; (3-[[3,5-dibromo-4-[4-hydroxy-3-(1-methylethyl)-phenoxy]-phenyl]-amino]-3-oxopropanoic acid)] in humans. In moderately overweight and hypercholesterolemic subjects KB2115 was found to be safe and well tolerated and elicited up to a 40% lowering of total and LDL cholesterol after 14 days of treatment. Bile acid synthesis was stimulated without evidence of increased cholesterol production, indicating that KB2115 induced net cholesterol excretion. KB2115 did not provoke detectable effects on the heart, suggesting that the pharmacological selectivity observed in animal models translates to humans. Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis.

The medical use of oxygen: a time for critical reappraisal

Oxygen treatment has been a cornerstone of acute medical care for numerous pathological states. Initially, this was supported by the assumed need to avoid hypoxaemia and tissue hypoxia. Most acute treatment algorithms, therefore, recommended the liberal use of a high fraction of inspired oxygen, often without first confirming the presence of a hypoxic insult. However, recent physiological research has underlined the vasoconstrictor effects of hyperoxia on normal vasculature and, consequently, the risk of significant blood flow reduction to the at‐risk tissue. Positive effects may be claimed simply by relief of an assumed local tissue hypoxia, such as in acute cardiovascular disease, brain ischaemia due to, for example, stroke or shock or carbon monoxide intoxication. However, in most situations, a generalized hypoxia is not the problem and a risk of negative hyperoxaemia‐induced local vasoconstriction effects may instead be the reality. In preclinical studies, many important positive anti‐inflammatory effects of both normobaric and hyperbaric oxygen have been repeatedly shown, often as surrogate end‐points such as increases in gluthatione levels, reduced lipid peroxidation and neutrophil activation thus modifying ischaemia–reperfusion injury and also causing anti‐apoptotic effects. However, in parallel, toxic effects of oxygen are also well known, including induced mucosal inflammation, pneumonitis and retrolental fibroplasia. Examining the available ‘strong’ clinical evidence, such as usually claimed for randomized controlled trials, few positive studies stand up to scrutiny and a number of trials have shown no effect or even been terminated early due to worse outcomes in the oxygen treatment arm. Recently, this has led to less aggressive approaches, even to not providing any supplemental oxygen, in several acute care settings, such as resuscitation of asphyxiated newborns, during acute myocardial infarction or after stroke or cardiac arrest. The safety of more advanced attempts to deliver increased oxygen levels to hypoxic or ischaemic tissues, such as with hyperbaric oxygen therapy, is therefore also being questioned. Here, we provide an overview of the present knowledge of the physiological effects of oxygen in relation to its therapeutic potential for different medical conditions, as well as considering the potential for harm. We conclude that the medical use of oxygen needs to be further examined in search of solid evidence of benefit in many of the current clinical settings in which it is routinely used.

Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation.

Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non‐invasive, more user‐independent and objective methods are available today. Limited portability, high cost, lack of robustness and non‐specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy‐to‐use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients.

Background: Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi‐centric, double‐blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation.

Pre-existing disease: the most important factor for health related quality of life long-term after critical illness: a prospective, longitudinal, multicentre trial

IntroductionThe aim of the present multicenter study was to assess long term (36 months) health related quality of life in patients after critical illness, compare ICU survivors health related quality of life to that of the general population and examine the impact of pre-existing disease and factors related to ICU care on health related quality of life.MethodsProspective, longitudinal, multicentre trial in three combined medical and surgical intensive care units of one university and two general hospitals in Sweden. By mailed questionnaires, health related quality of life was assessed at 6, 12, 24 and 36 months after the stay in ICU by EQ-5D and SF-36, and information of pre-existing disease was collected at the 6 months measure. ICU related factors were obtained from the local ICU database. Comorbidity and health related quality of life (EQ-5D; SF-36) was examined in the reference group. Among the 5306 patients admitted, 1663 were considered eligible (>24 hrs in the intensive care unit, and age ≥ 18 yrs, and alive 6 months after discharge). At the 6 month measure 980 (59%) patients answered the questionnaire. Of these 739 (75%) also answered at 12 month, 595 (61%) at 24 month, and 478 (47%) answered at the 36 month measure. As reference group, a random sample (n = 6093) of people from the uptake area of the hospitals were used in which concurrent disease was assessed and adjusted for.ResultsOnly small improvements were recorded in health related quality of life up to 36 months after ICU admission. The majority of the reduction in health related quality of life after care in the ICU was related to the health related quality of life effects of pre-existing diseases. No significant effect on the long-term health related quality of life by any of the ICU-related factors was discernible.ConclusionsA large proportion of the reduction in the health related quality of life after being in the ICU is attributable to pre-existing disease. The importance of the effect of pre-existing disease is further supported by the small, long term increment in the health related quality of life after treatment in the ICU. The reliability of the conclusions is supported by the size of the study populations and the long follow-up period.

Acute kidney injury is common, parallels organ dysfunction or failure, and carries appreciable mortality in patients with major burns: a prospective exploratory cohort study

IntroductionThe purpose of this study was to determine the incidence, time course, and outcome of acute kidney injury after major burns and to evaluate the impact of possible predisposing factors (age, gender, and depth and extent of injury) and the relation to other dysfunctioning organs and sepsis.MethodWe performed an explorative cohort study on patients with a TBSA% (percentage burned of total body surface area) of 20% or more who were admitted to a national burn centre. Acute kidney injury was classified according to the international consensus classification of RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease). Prospectively collected clinical and laboratory data were used for assessing organ dysfunction, systemic inflammatory response, and sepsis.ResultsThe incidence of acute kidney injury among major burns was 0.11 per 100,000 people per year. Of 127 patients, 31 (24%) developed acute kidney injury (12% Risk, 8% Injury, and 5% Failure). Mean age was 40.6 years (95% confidence interval [CI] 36.7 to 44.5), TBSA% was 38.6% (95% CI 35.5% to 41.6%), and 25% were women. Mortality was 14% and increased with increasing RIFLE class (7% normal, 13% Risk, 40% Injury, and 83% Failure). Renal dysfunction occurred within 7 days in 55% of the patients and recovered among all survivors. Age, TBSA%, and extent of full thickness burns were higher among the patients who developed acute kidney injury. Pulmonary dysfunction and systemic inflammatory response syndrome were present in all of the patients with acute kidney injury and developed before the acute kidney injury. Sepsis was a possible aggravating factor in acute kidney injury in 48%. Extensive deep burns (25% or more full thickness burn) increased the risk for developing acute kidney injury early (risk ratio 2.25).ConclusionsAcute kidney injury is common, develops soon after the burn, and parallels other dysfunctioning organs. Although acute kidney injury recovered in all survivors, in higher acute kidney injury groups, together with cardiovascular dysfunction, it correlated with mortality.

Assessment of incidence of severe sepsis in Sweden using different ways of abstracting International Classification of Diseases codes: difficulties with methods and interpretation of results.

Objective:To compare three International Classification of Diseases code abstraction strategies that have previously been reported to mirror severe sepsis by examining retrospective Swedish national data from 1987 to 2005 inclusive. Design:Retrospective cohort study. Setting:Swedish hospital discharge database. Patients:All hospital admissions during the period 1987 to 2005 were extracted and these patients were screened for severe sepsis using the three International Classification of Diseases code abstraction strategies, which were adapted for the Swedish version of the International Classification of Diseases. Two code abstraction strategies included both International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes, whereas one included International Classification of Diseases, Tenth Revision codes alone. Interventions:None. Measurements and Main Results:The three International Classification of Diseases code abstraction strategies identified 37,990, 27,655, and 12,512 patients, respectively, with severe sepsis. The incidence increased over the years, reaching 0.35 per 1000, 0.43 per 1000, and 0.13 per 1000 inhabitants, respectively. During the International Classification of Diseases, Ninth Revision period, we found 17,096 unique patients and of these, only 2789 patients (16%) met two of the code abstraction strategy lists and 14,307 (84%) met one list. The International Classification of Diseases, Tenth Revision period included 46,979 unique patients, of whom 8% met the criteria of all three International Classification of Diseases code abstraction strategies, 7% met two, and 84% met one only. Conclusions:The three different International Classification of Diseases code abstraction strategies generated three almost separate cohorts of patients with severe sepsis. Thus, the International Classification of Diseases code abstraction strategies for recording severe sepsis in use today provides an unsatisfactory way of estimating the true incidence of severe sepsis. Further studies relating International Classification of Diseases code abstraction strategies to the American College of Chest Physicians/Society of Critical Care Medicine scores are needed.

Thiopentone or propofol for induction of isoflurane-based anaesthesia for ambulatory surgery?

This study compares psychomotor recovery following induction of anaesthesia with either thiopentone or propofol in 30 healthy, unpremedicated patients undergoing outpatient arthroscopic procedures of the knee. A battery of tests including simple reaction time (SRT), choice reaction time (CRT), perceptive accuracy test (PAT) and digit symbol substitution test (DSST) were done before anaesthesia. The patients were randomly divided into two groups: Group 1 was induced with thiopentone 5–6 mg/kg while Group 2 was induced with propofol 2–3 mg/kg. Anaesthesia was then maintained with isoflurane (0.5–2%) in oxygen and air, and supplements of alfentanil were given for analgesia during spontaneous respiration with a face mask. Psychomotor recovery assessed every 30 min postoperatively for 120 min showed that patients in Group 1 had not returned to baseline values until 120 min after the operation on the PAT, while those in Group 2 had returned to baseline values at 60 min. No patient had any significant side effects. The SRT, CRT and DSST proved to be relatively insensitive in the detection of residual effects of anaesthesia and had a significant learning effect. This study suggests that induction of anaesthesia with propofol followed by maintenance with isoflurane in oxygen and air during spontaneous ventilation is associated with rapid psychomotor recovery and is a suitable method for ambulatory surgery. The PAT is sensitive and not associated with some of the problems found with other commonly used tests.

Prevalence of sleep disturbances and long-term reduced health-related quality of life after critical care: a prospective multicenter cohort study

IntroductionThe aim of the present prospective multicenter cohort study was to examine the prevalence of sleep disturbance and its relation to the patients reported health-related quality of life after intensive care. We also assessed the possible underlying causes of sleep disturbance, including factors related to the critical illness.MethodsBetween August 2000 and November 2003 we included 1,625 consecutive patients older than 17 years of age admitted for more than 24 hours to combined medical and surgical intensive care units (ICUs) at three hospitals in Sweden. Conventional intensive care variables were prospectively recorded in the unit database. Six months and 12 months after discharge from hospital, sleep disturbances and the health-related quality of life were evaluated using the Basic Nordic Sleep Questionnaire and the Medical Outcomes Study 36-item Short-form Health Survey, respectively. As a nonvalidated single-item assessment, the quality of sleep prior to the ICU period was measured. As a reference group, a random sample (n = 10,000) of the main intake area of the hospitals was used.ResultsThe prevalence of self-reported quality of sleep did not change from the pre-ICU period to the post-ICU period. Intensive care patients reported significantly more sleep disturbances than the reference group (P < 0.01). At both 6 and 12 months, the main factor that affected sleep in the former hospitalised patients with an ICU stay was concurrent disease. No effects were related to the ICU period, such as the Acute Physiology and Chronic Health Evaluation score, the length of stay or the treatment diagnosis. There were minor correlations between the rate and extent of sleep disturbance and the health-related quality of life.ConclusionThere is little change in the long-term quality of sleep patterns among hospitalised patients with an ICU stay. This applies both to the comparison before and after critical care as well as between 6 and 12 months after the ICU stay. Furthermore, sleep disturbances for this group are common. Concurrent disease was found to be most important as an underlying cause, which emphasises that it is essential to include assessment of concurrent disease in sleep-related research in this group of patients.