Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment

Background  Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU). Objective and methods  To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion. Results and conclusions  Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole (<30 days). In contrast, pre-emptive therapy is based on the presence of surrogate markers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Part I is published at: doi:.     

Assisted breathing is better in acute respiratory failure

PURPOSE OF REVIEW: Mechanical ventilation is usually provided in acute lung injury to ensure alveolar ventilation and reduce the patients' work of breathing without further damaging the lungs by the treatment itself. Although partial ventilatory support modalities were initially developed for weaning from mechanical ventilation, they are increasingly used as primary modes of ventilation, even in patients in the acute phase of pulmonary dysfunction. The aim of this paper is to review the role of spontaneous breathing ventilatory modalities with respect to their physiologic or clinical evidence. RECENT FINDINGS: By allowing patients with acute lung injury to breathe spontaneously, one can expect improvement in gas exchange and in systemic blood flow, on the basis of both experimental and clinical trials. In addition, by increasing end-expiratory lung volume, as will occur when airway pressure release ventilation is used, recruitment of collapsed or consolidated lung is likely to occur, especially in juxtadiaphragmatic lung regions. Until recently, traditional approaches to mechanical ventilatory support of patients with acute lung injury have called for adaptation of the patient to the mechanical ventilator using heavy sedation and administration of neuromuscular blocking agents. Recent investigations have questioned the utility of sedation, muscle paralysis, and mechanical control of ventilation. Further, evidence exists that lowering sedation levels will decrease the duration of mechanical ventilatory support, the length of stay in the intensive care unit, and the overall costs of hospitalization. SUMMARY: On the basis of currently available data, the authors suggest the use of techniques of mechanical ventilatory support that maintain, rather than suppress, spontaneous ventilatory effort, especially in patients with severe pulmonary dysfunction.     

Cardiorespiratory Effects of Automatic Tube Compensation during Airway Pressure Release Ventilation in Patients with Acute Lung Injury

Background: Spontaneous breaths during airway pressure release ventilation (APRV) have to overcome the resistance of the artificial airway. Automatic tube compensation provides ventilatory assistance by increasing airway pressure during inspiration and lowering airway pressure during expiration, thereby compensating for resistance of the artificial airway. The authors studied if APRV with automatic tube compensation reduces the inspiratory effort without compromising cardiovascular function, end-expiratory lung volume, and gas exchange in patients with acute lung injury.

Methods: Fourteen patients with acute lung injury were breathing spontaneously during APRV with or without automatic tube compensation in random order. Airway pressure, esophageal and abdominal pressure, and gas flow were continuously measured, and tracheal pressure was estimated. Trans-diaphragmatic pressure time product was calculated. End-expiratory lung volume was determined by nitrogen washout. The validity of the tracheal pressure calculation was investigated in seven healthy ventilated pigs.

Results: Automatic tube compensation during APRV increased airway pressure amplitude from 7.7 +/- 1.9 to 11.3 +/- 3.1 cm H2O (mean +/- SD;P < 0.05) while decreasing trans-diaphragmatic pressure time product from 45 +/- 27 to 27 +/- 15 cm H2O [middle dot] s-1 [middle dot] min-1 (P < 0.05), whereas tracheal pressure am-plitude remained essentially unchanged (10.3 +/- 3.5 vs. 10.1 +/- 3.5 cm H2O). Minute ventilation increased from 10.4 +/- 1.6 to 11.4 +/- 1.5 l/min (P < 0.001), decreasing arterial carbon dioxide tension from 52 +/- 9 to 47 +/- 6 mmHg (P < 0.05) without affecting arterial blood oxygenation or cardiovascular function. End-expiratory lung volume increased from 2,806 +/- 991 to 3,009 +/- 994 ml (P < 0.05). Analysis of tracheal pressure-time curves indicated nonideal regulation of the dynamic pressure support during automatic tube compensation as provided by a standard ventilator.     

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

Summary 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. Received: 19 December 2000 Accepted: 9 January 2001     

Vorteile der assistierten Spontanatmung

Summary Spontaneous breathing with Biphasic Positive Airway Pressure (BIPAP) or Airway Pressure Release Ventilation (APRV) caused a reduction in intrapulmonary shunting and dead space ventilation and improvement in arterial oxygenation in patients with acute respiratory distress syndrome. During spontaneous breathing with APRV/BIPAP venous return, cardiac output and oxygen delivery increased while oxygen consumption remained unchanged. In patients early spontaneous breathing with APRV/BIPAP was associated with a better arterial oxygenation than in patients receiving controlled mechanical ventilation for 3 days and were then weaned with APRV/BIPAP. Length of mechanical ventilation, intubation and ICU stay was shorter in patients breathing spontaneously early with APRV/BIPAP. Therefore, early spontaneous breathing with APRV/BIPAP may be of advantage. Zusammenfassung Spontanatmung unter Biphasic Positive Airway Pressure (BIPAP) oder Airway Pressure Release Ventilation (APRV) führt bei Patienten mit akutem Lungenversagen zu einer Reduktion des Blutflusses zu nicht ventilierten Shuntarealen, der Totraumventilation und einer Zunahme des PaO₂. Bedingt durch die Spontanatmung nahm der venöse Rückstrom, das Herzzeitvolumen und die Sauerstofftransportkapazität zu, ohne daß der Sauerstoffverbrauch stieg. Bei Patienten, die unter APRV/BIPAP frühzeitig spontan atmeten, war der Gasaustausch signifikant besser als bei den Patienten, die zunächst drei Tage kontrolliert beatmet und anschließend mittels APRV/BIPAP entwöhnt wurden. Die Dauer der maschinellen Beatmung, der Intubation und des Intensivaufenthaltes waren bei Patienten, die frühzeitig unter APRV/BIPAP spontan atmeten, signifikant kürzer. APRV/BIPAP scheint als primäre Unterstützung einer insuffizienten Spontanatmung vorteilhaft zu sein.     

Effect of Low Isoflurane Concentrations on the Ventilation-Perfusion Distribution in Injured Canine Lungs

Background: Rapid recovery and weaning from ventilatory support and cardiovascular stability are suggested advantages of isoflurane inhalation, in concentrations ranging from 0.1 to 0.6 vol%, for long-term sedation in mechanical ventilated patients. This study was designed to determine whether isoflurane in low concentrations impairs pulmonary gas exchange by increasing ventilation and perfusion ([latin capital V with dot above]A/[Latin capital letter Q with dot above]) mismatch during lung injury.

Methods: Fourteen anesthetized dogs received in random order 0, 0.25, or 0.5 vol% end-tidal isoflurane before and after induction of lung injury with oleic acid. Gas exchange was assessed by blood gas analysis and by estimating the [latin capital V with dot above]A/[Latin capital letter Q with dot above] distributions using the multiple inert gas elimination technique.

Results: Administration of oleic acid produced a lung injury with severe [latin capital V with dot above]A/[Latin capital letter Q with dot above] mismatch and 38 +/- 4% intrapulmonary shunting of blood. During lung injury, isoflurane accounted for a dose-related increase in blood flow to shunt units from 38 +/- 4 to 42 +/- 3 (0.25 vol%) and 48 +/- 4% (0.5 vol%) (P < 0.05), dispersion pulmonary blood flow distribution from 0.94 +/- 0.07 to 1.01 +/- 0.09 (0.25 vol%) and 1.11 +/- 0.11% (0.5 vol%) (P < 0.05), and a decrease in perfusion of normal [latin capital V with dot above]A/[Latin capital letter Q with dot above] units from 58 +/- 5 to 55 +/- 4 (0.25 vol%) and 50 +/- 4% (0.5 vol%) (P < 0.05) (mean +/- SE). Isoflurane decreased arterial oxygen partial pressure from 72 +/- 4 to 62 +/- 4 mmHg (0.25 vol%) and 56 +/- 4 mmHg (0.5 vol%) (P < 0.05) and oxygen delivery from 573 +/- 21 to 529 +/- 19 ml [middle dot] kg-1 [middle dot] min-1 (0.25 vol%) and 505 +/- 22 ml [middle dot] kg-1 [middle dot] min-1 (0.5 vol%) (P < 0.05). Gas exchange, perfusion of shunt and normal [latin capital V with dot above]A/[Latin capital letter Q with dot above] units, and pulmonary blood flow distribution was similar in absence of lung injury with and without isoflurane. Isoflurane 0.5 vol% lowered cardiac output during all conditions (P < 0.05).