Plasma levels of macrophage migration inhibitory factor are elevated in patients with severe sepsis

OBJECTIVE: To investigate the role of macrophage migration inhibitory factor (MIF) as a marker of severity of systemic inflammation in patients with severe sepsis and critically ill postsurgical patients. DESIGN: Prospective observational study in consecutive patients with severe sepsis, critically ill nonseptic postsurgical patients, and healthy blood donors. SETTING: A surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 19 patients with severe sepsis, 18 critically ill nonseptic postsurgical patients, and 10 healthy blood donors. MEASUREMENTS AND RESULTS: MIF plasma levels of patients and participants were measured. Interleukin 6 plasma levels were monitored as a control marker of inflammation. The median MIF plasma level was four to five times higher in patients with severe sepsis (2.70 ng/ml, range 0.31-19.59) and in critically ill nonseptic postsurgical patients (2.43 ng/ml, range 0.49-4.31) than in healthy blood donors (0.56 ng/ml, range 0.16-1.68). MIF plasma levels did not differ between the patient groups. CONCLUSIONS: MIF serves as a general marker for systemic inflammation in septic and nonseptic acute critical illness, but MIF does not discriminate for severity or differentiate between infectious and noninfectious origins of an acute critical illness.     

Comparison of postoperative respiratory function after laparoscopy or open laparotomy for cholecystectomy.

Cholecystectomy performed via laparotomy is associated with reduction of lung volumes including functional residual capacity that may lead to postoperative hypoxia and atelectasis. Laparoscopic cholecystectomy is associated with faster recovery compared to open laparotomy and cholecystectomy. To determine whether laparoscopic cholecystectomy was associated with less pulmonary dysfunction, 20 patients (ASA Physical Status I) undergoing elective cholecystectomy were randomly assigned to surgical teams performing either laparoscopy or open laparotomy for cholecystectomy. Patients in whom one or the other surgical technique had to be performed for medical or psychologic indications were excluded from the study. A standardized anesthetic technique and postoperative analgesic regimen were used. Forced vital capacity and forced expiratory volume in 1 s; functional residual capacity determined by a closed-circuit, constant volume helium dilution technique; and arterial O2 and CO2 tensions were measured preoperatively and at 6, 24, and 72 h postcholecystectomy. Forced vital capacity and forced expiratory volume in 1 s were significantly greater (P less than 0.05) in the laparoscopy compared to the laparotomy group at 6, 24, and 72 h postoperatively. Forced vital capacity relative to preoperative values was significantly (P less than 0.05) greater in patients with laparoscopy (24 h, 70 +/- 14%; 72 h, 91 +/- 6%) compared to open laparotomy (24 h, 57 +/- 23%; 72 h, 77 +/- 14%). Similarly, forced expiratory volumes in 1 s relative to preoperative values were significantly (P less than 0.05) greater in patients with laparoscopy (24 h, 85 +/- 13%; 72 h, 92 +/- 9%) compared to open laparotomy (24 h, 54 +/- 22%; 72 h, 77 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased susceptibility to apoptosis in circulating lymphocytes of critically ill patients

BACKGROUND AND AIMS: Lymphocyte apoptosis may influence immune responsiveness in systemic inflammation. Therefore, we investigated whether early signs of apoptosis (i.e., annexin-V binding and cell shrinkage) in peripheral lymphocytes were different among patients with severe sepsis, critically ill, nonseptic patients after major surgery, and healthy individuals. PATIENTS/METHODS: Ten patients with severe sepsis and ten critically ill, nonseptic patients after major surgery admitted to a surgical intensive care unit in a university hospital were included in the study. In addition, ten healthy blood donors were included for comparison. We investigated early signs of apoptosis using flow cytometric measurement of annexin-V binding to the cell surface and cell shrinkage of peripheral lymphocytes. RESULTS: The percentage of apoptotic lymphocytes determined as annexin-V positive and propidium iodide negative cells was increased in freshly prepared cells of patients with severe sepsis (11.4 +/- 0.5%) and critically ill, nonseptic patients after major surgery (18.5 +/- 2.0%) relative to healthy blood donors (4.4 +/- 0.5%) (P < 0.05). No significant difference between patients with severe sepsis and patients after major surgery were found. Annexin-V binding increased significantly after OKT-3 stimulation of lymphocytes in patients with severe sepsis (34.4 +/- 1.6%), patients after major surgery (33.8 +/- 3.4%), and healthy blood donors (21.1 +/- 2.8%). No significant difference among groups was detected following OKT-3 stimulation. Furthermore, freshly isolated peripheral lymphocytes of patients with severe sepsis and critically ill, nonseptic patients after major surgery revealed a significantly higher proportion of cell shrinkage than in healthy blood donors (55.0 +/- 2.2%, 21.5 +/- 2.4% vs 3.6 +/- 0.7%; P < 0.05). CONCLUSION: Circulating lymphocytes of critically ill patients show a high degree of early signs of cellular apoptosis. This may contribute to hyporesponsiveness of immune cells in systemic inflammation.     

Biphasic positive airway pressure (BIPAP)--a new form of augmented ventilation

Two modes of combining spontaneous breathing and mechanical ventilation are already in use: periodic mechanical support always followed by a period of spontaneous breathing (intermittent mandatory ventilation; IMV) and mechanical support of each spontaneous breath (inspiratory assistance; IA). Biphasic positive airway pressure (BIPAP), in contrast, is based on neither of the above mentioned principles. It is rather a mixture of pressure controlled (PC) ventilation and spontaneous breathing, which is unrestricted in each phase of the respiratory cycle. The BIPAP circuit switches between a high (Phi) and a low (Plo) airway pressure level in an adjustable time sequence. At both pressure levels the patient can breathe spontaneously in a continuous positive airway pressure system (CPAP). The volume displacement caused by the difference between Phi and Plo and the BIPAP frequency (F) contribute the mechanical ventilation to total ventilation. Duration of the Phi and the Plo phases can be independently adjusted. Similar to the I:E ratio during controlled ventilation, the phase time ratio (PhTR) is calculated as the ratio between the durations of the two pressure phases. A PhTR greater than 1:1 is called IR-BIPAP. A BIPAP system can be set up either as a continuous flow system, or as a demand valve system. A continuous-flow BIPAP system consists of a high-flow CPAP system, a reservoir bag, and a pneumatically controlled membrane valve in the expiratory limb. A magnetic valve operated by an impulse generator switches between Phi and Plo, controlling the pop-off pressures of the expiratory valve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Somatotropic axis dysfunction in critically ill patients: altered response to growth hormone-releasing hormone

The aim of this study was to investigate the pituitary‘s capacity to release growth hormone (GH) in critically ill patients by stimulation with GH-releasing hormone (GHRH). Thirty-two patients with severe sepsis and 20 critically ill, nonseptic patients after major surgery were studied in the setting of a surgical intensive care unit. Nine healthy individuals without clinical signs of disturbance of the somatotropic hypothalamic-pituitary axis were included for comparison. The pituitary‘s capacity to release GH was tested with an intravenous bolus injection of 1μg per kg body weight GHRH (Ferring, Kiel, Germany). The median basal plasma GH level was comparable in all groups studied. In contrast, the median peak plasma GH level was significantly lower in critically ill, nonseptic patients after major surgery (5.1, range 1.3–131.0ng/ml, n=20) compared to healthy individuals (23.2, range 12.8–35.2 ng/ml, n=9) (p<>;0.01). However, the median peak plasma GH level in patients with severe sepsis (15.3, range 1.6–111.5ng/ml, n=32) was not significantly different compared to healthy individuals (23.2, range 12.8–35.2ng/ml, n=9) (p>>;0.05). The median plasma insulin-like growth factor-I (IGF-I) level was significantly decreased in patients with severe sepsis (32.0, range 32.0–150.0ng/ml, n=32) and in critically, ill, nonseptic patients after major surgery (50.0, range 32.0–144.0ng/ml, n=20) compared to healthy individuals (229.0, range 129.0–503.0ng/ml, n=9) (p<>;0.001). No significant difference was found between patients after major surgery and patients with severe sepsis. In conclusion, a low level of circulating IGF-I was associated with the pituitary‘s low capacity to release GH in critically ill, nonseptic patients after major surgery, whereas patients with severe sepsis had a widespread range of pituitary capacity to release GH associated with low IGF-I levels. The pathophysiological basis for not secreting stored GH during critical illness is at present unclear. The treatment with high doses of human GH has been shown to attenuate the catabolic response to injury, surgery and sepsis, whereas in patients with severe sepsis GH administration bypasses its pituitary storage and may trigger a hyperinflammatory response. However, critically ill nonseptic patients after major surgery may profit from GH treatment since they possess a low pituitary capacity to release GH. Thus, performing a GHRH test might facilitate the decision for treatment with human GH.     

Mechanical ventilation strategies and inflammatory responses to cardiac surgery: a prospective randomized clinical trial

Objective To examine whether postoperative mechanical ventilation with lower tidal volumes (V_T) has protective effects on inflammatory responses induced by cardiopulmonary bypass (CPB) surgery in smokers and nonsmokers.Design and setting Prospective, randomized, controlled clinical trial in the intensive care unit of a university hospital.Patients and participants We examined 44 patients (22 smokers, 22 nonsmokers) immediately after uncomplicated CPB surgery.Interventions Ventilation was applied for 6 h with either V_T of either 6 or 12 ml/kg ideal body weight.Measurements and results The time course of serum tumor necrosis factor (TNF) , interleukin (IL) 6, and IL-8 determined 0, 2, 4, and 6 h after randomization did not differ significantly between the ventilatory strategies. By contrast, in bronchoalveolar lavage fluids sampled after 6 h only TNF- levels were significantly higher in the high V_T group than the low V_T group (50±111 pg/ml vs. 1±7 pg/ml). IL-6 and IL-8 concentrations did not differ between groups. Subgroup analysis of patients with serum TNF- level higher than 0 pg/ml after surgery revealed lower TNF- serum levels during lower V_T ventilation. All observed effects were small, independent of patients history of smoking, and were not correlated with duration of ventilation and ICU stay.Conclusions Ventilation with lower V_T had no or only minor effect on systemic and pulmonary inflammatory responses in patients with healthy lungs after uncomplicated CPB surgery. Our data do not suggest a clinical benefit of using low V_T ventilation in these selected patients.This study was supported by grants from the BONFOR Forschungsförderung (project O-117.0006), University of Bonn, Germany, and from the Deutsche Forschungsgemeinschaft (Pu 219/1-1, and Uh 88/4-1), Bonn, Germany, and by departmental funding.     

Remifentanil for analgesia-based sedation in the intensive care unit

Providing effective analgesia and adequate sedation is a generally accepted goal of intensive care medicine. Due to its rapid, organ independent and predictable metabolism the short acting opioid remifentanil might be particularly useful for analgesia-based sedation in the intensive care unit (ICU). This hypothesis was tested by two studies in this issue of Critical Care. The study by Breen et al. shows that remifentanil does not exert prolonged clinical effects when continuously infused in renal failure patients, although the weak acting metabolite remifentanil acid accumulates. The study by Muellejans et al. reports a multicenter trial comparing a remifentanil versus a fentanyl based regimen in ICU patients. With both substances a target analgesia and sedation level was reached, and no major differences were found when frequent assessments of the sedation level and according readjustments of doses were performed. These results are in accordance with other studies suggesting that the adherence to a clear analgesia-based sedation protocol might be more important then the choice of medications itself.