[Atelectasis during general anaesthesia - mechanisms and importance]. / Atelektaser under anestesi ­ uppkomst och betydelse.

In 1985, Dr. Göran Hedenstierna pioneered in the transition of atelectases during anaesthesia from a concept to a clinical entity, using computed tomography to detect "pulmonary densities". These densities were soon to be fully recognized as atelectasis. Most of the conclusions in the original paper are almost 40 years later still scientifically intact: the immediate appearance of atelectasis after induction of anaesthesia in the majority of adult patients, that atelectasis impedes arterial oxygenation by shunting deoxygenated blood, and the efficacy of a positive end-expiratory pressure to oppose atelectasis. The importance of atelectasis in the development of postoperative pulmonary complications is still obscure, as is the concept of protective ventilation. A common denominator in several studies on protective ventilation during anaesthesia is the lack of recognising the importance of the oxygen concentration. The pivotal role of oxygen in the development of atelectasis, and the impact of oxygen in relation to different conditions in the lungs, needs further studies.

Higher age and obesity limit atelectasis formation during anaesthesia: an analysis of computed tomography data in 243 subjects.

BACKGROUND: General anaesthesia is increasingly common in elderly and obese patients. Greater age and body mass index (BMI) worsen gas exchange. We assessed whether this is related to increasing atelectasis during general anaesthesia. METHODS: This primary analysis included pooled data from previously published studies of 243 subjects aged 18-78 yr, with BMI of 18-52 kg m-2. The subjects had no clinical signs of cardiopulmonary disease, and they underwent computed tomography (CT) awake and during anaesthesia before surgery after preoxygenation with an inspired oxygen fraction (FIO2) of >0.8, followed by mechanical ventilation with FIO2 of 0.3 or higher with no PEEP. Atelectasis was assessed by CT. RESULTS: Atelectasis area of up to 39 cm2 in a transverse scan near the diaphragm was seen in 90% of the subjects during anaesthesia. The log of atelectasis area was related to a quadratic function of (age+age2) with the most atelectasis at ∼50 yr (r2=0.08; P<0.001). Log atelectasis area was also related to a broken-line function of the BMI with the knee at 30 kg m-2 (r2=0.06; P<0.001). Greater atelectasis was seen in the subjects receiving FIO2 of 1.0 than FIO2 of 0.3-0.5 (12.8 vs 8.1 cm2; P<0.001). A multiple regression analysis, including a quadratic function of age, a broken-line function of the BMI, and dichotomised FIO2 (0.3-0.5/1.0) adjusting for ventilatory frequency, strengthened the association (r2=0.23; P<0.001). PaO2 decreased with both age and BMI. CONCLUSIONS: Atelectasis during general anaesthesia increased with age up to 50 yr and decreased beyond that. Atelectasis increased with BMI in normal and overweight patients, but showed no further increase in obese subjects (BMI ≥30 kg m-2). Therefore, greater age and obesity appear to limit atelectasis formation during general anaesthesia.

Oxygenation Impairment during Anesthesia: Influence of Age and Body Weight.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: During anesthesia oxygenation is impaired, especially in the elderly or obese, but the mechanisms are uncertain. WHAT THIS ARTICLE TELLS US THAT IS NEW: Pooled data were examined from 80 patients studied with multiple inert gas elimination technique and computed tomography. Oxygenation was impaired by anesthesia, more so with greater age or body mass index. The key contributors were low ventilation/perfusion ratio (likely airway closure) in the elderly and shunt (atelectasis) in the obese. BACKGROUND: Anesthesia is increasingly common in elderly and overweight patients and prompted the current study to explore mechanisms of age- and weight-dependent worsening of arterial oxygen tension (PaO2). METHODS: This is a primary analysis of pooled data in patients with (1) American Society of Anesthesiologists (ASA) classification of 1; (2) normal forced vital capacity; (3) preoxygenation with an inspired oxygen fraction (FIO2) more than 0.8 and ventilated with FIO2 0.3 to 0.4; (4) measurements done during anesthesia before surgery. Eighty patients (21 women and 59 men, aged 19 to 69 yr, body mass index up to 30 kg/m2) were studied with multiple inert gas elimination technique to assess shunt and perfusion of poorly ventilated regions (low ventilation/perfusion ratio [(Equation is included in full-text article.)]) and computed tomography to assess atelectasis. RESULTS: PaO2/FIO2 was lower during anesthesia than awake (368; 291 to 470 [median; quartiles] vs. 441; 397 to 462 mm Hg; P = 0.003) and fell with increasing age and body mass index. Log shunt was best related to a quadratic function of age with largest shunt at 45 yr (r2 =0.17, P = 0.001). Log shunt was linearly related to body mass index (r2 = 0.15, P < 0.001). A multiple regression analysis including age, age2, and body mass index strengthened the association further (r2 = 0.27). Shunt was highly associated to atelectasis (r2 = 0.58, P < 0.001). Log low (Equation is included in full-text article.)showed a linear relation to age (r2 = 0.14, P = 0.001). CONCLUSIONS: PaO2/FIO2 ratio was impaired during anesthesia, and the impairment increased with age and body mass index. Shunt was related to atelectasis and was a more important cause of oxygenation impairment in middle-aged patients, whereas low(Equation is included in full-text article.), likely caused by airway closure, was more important in elderly patients. Shunt but not low(Equation is included in full-text article.)increased with increasing body mass index. Thus, increasing age and body mass index impaired gas exchange by different mechanisms during anesthesia.

Pronounced elevation of resistin correlates with severity of disease in severe sepsis and septic shock.

OBJECTIVE: Resistin induces insulin resistance in mice. In humans, recent data suggest that resistin functions as a proinflammatory cytokine. Here, we studied resistin up to 2 wks after admission in patients with septic shock and/or severe sepsis. DESIGN: Two prospective studies of patients with sepsis and in vitro studies of resistin interaction with monocytes. SETTING: Intensive care unit at Karolinska University Hospital and Center for Infectious Medicine, Karolinska Institute, Huddinge, Sweden. PATIENTS: Twenty-nine patients with severe sepsis and 66 with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-five patients were studied, 25 of whom died within 28 days. Resistin and cytokine levels and routine biochemistry were measured at three to six defined time points during the first 2 wks after admission and were correlated to other cytokines, glucose levels, body mass index, Acute Physiology and Chronic Health Evaluation II, and Sepsis-related Organ Failure Assessment scores. Serum resistin was significantly elevated compared with healthy controls (p < .000001) and correlated with severity of disease as measured by Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores, with an increasingly strong degree of correlation over time. Median levels were four- to eight-fold higher than controls and remained high up to 2 wks after admission to the intensive care unit. Levels correlated with interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-alpha, creatinine, D-dimer, and lactate, but not with p-glucose or body mass index. In vitro, resistin was released from monocytes after stimulation with either lipopolysaccharide or high mobility group box 1 protein. Recombinant resistin itself up-regulated intercellular adhesion molecule-1 on monocytes. CONCLUSIONS: This is the first study assessing systemic levels of resistin in patients with septic shock/severe sepsis. We show that resistin is a marker of severity of disease and possibly a mediator of the prolonged inflammatory state seen in infected critically ill patients. Further exploration of resistin as a therapeutic target and marker of disease is merited.

Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock.

OBJECTIVE: To study the systemic release and kinetics of high mobility group box-1 protein (HMGB1) in relation to clinical features in a population of patients with severe sepsis or septic shock and to compare these with the kinetics of the cytokines interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha. DESIGN: Prospective study of two cohorts of patients. SETTING: Intensive care unit and infectious disease clinic at Karolinska University Hospital Huddinge. PATIENTS: Twenty-six patients with severe sepsis, 33 patients with septic shock, and a reference group of five patients with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-four patients were included, ten of whom died within 28 days. Cytokine levels were measured at five time points during the first week after admission and were correlated to Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Two HMGB1 assays were used. Both demonstrated delayed kinetics for HMGB1 with high levels on inclusion that remained high throughout the study period. Serum concentration at 144 hrs, the last sampling point, was 300 times higher, 34,000 +/- 76,000 pg/mL (mean +/- sd), than any of the other cytokines. This study, however, found no predictable correlation between serum levels of HMGB1 and severity of infection. We did quite unexpectedly find significantly lower levels of HMGB1 in nonsurvivors compared with survivors as measured by our main assay, but the other showed no difference between the two groups. Levels of interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-alpha correlated significantly with severity of disease, and all were significantly higher in patients with septic shock compared with those with severe sepsis. Neither of these comparisons showed significant correlations for HMGB1. CONCLUSIONS: This is the first prospective study assessing the release over time of HMGB1 in a population of patients with sepsis, severe sepsis, or septic shock. Levels remained high in the majority of patients up to 1 wk after admittance, indicating that the cytokine indeed is a downstream and late mediator of inflammation. Further studies are required to fully define the relationship of HMGB1 to severity of disease.

The pharmacokinetics of ketobemidone in critically ill patients.

AIMS: To study the pharmacokinetics of orally and intravenously administered ketobemidone in critically ill patients. METHODS: Seventeen patients were studied during their stay in the intensive care unit at Huddinge University Hospital. Nine patients received a single intravenous dose of ketobemidone (0.04 mg kg-1) and eight patients received a single oral dose of 5 mg. Plasma concentrations of ketobemidone were measured using liquid chromatography-mass spectrometry. The pharmacokinetic analysis was performed using WinNonlin trade mark software. RESULTS: There was a wide variation in the different pharmacokinetic parameters among patients. Mean clearance in patients treated intravenously was 74.5 (95% CI 43.2, 128.3) and mean Vd was 2.4 l kg-1 (95% CI 2.0, 2.8). t1/2,z also varied widely with a mean value of 4.41 h (95% CI 2.7, 7.0). The corresponding values for MRT were 5.4 and 3.3, 8.8. Mean oral clearance (CL/F) was 102 l h-1 (95% CI 82.7, 125.8), mean Vz/F was 11.2 l kg-1 (95% CI 9.7, 13.1) and mean t1/2,z was 6.0 (95% CI 4.9, 7.3) in orally treated patients. Cmax showed a mean of 38 nmol l-1 (95% CI of 31, 47). A significant correlation was observed between the glomerular filtration rate (GFR) and the half-life of ketobemidone (r = -0.72, P < 0.05). t1/2,z was generally longer and the variation larger in critically ill patients compared with healthy individuals. However, there was no correlation between the elimination of ketobemidone in critically ill patients and plasma C-reactive protein, white blood count or plasma albumin concentrations. CONCLUSIONS: The disposition of ketobemidone is highly variable in critically ill patients. In order to ensure sufficient analgesia and avoid toxicity, therapeutic monitoring should be employed when using ketobemidone in this group of patients.