Alain-Michel Dive

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease

Aspergillus spp. cultured in specimens from the airways of chronic obstructive pulmonary disease (COPD) patients are frequently considered as a contaminant. However, growing evidence suggests that severe COPD patients are at higher risk of developing invasive pulmonary aspergillosis (IPA), although IPA incidence in this population is poorly documented. Some data report that COPD is the underlying disease in 1% of patients with IPA. Definitive diagnosis of IPA in COPD patients is often difficult as tissue samples are rarely obtained before death. Diagnosis is therefore usually based on a combination of clinical features, radiological findings (mostly thoracic computed tomography scans), microbiological results and, sometimes, serological information. Of 56 patients with IPA reported in the literature, 43 (77%) were receiving corticosteroids on admission to hospital. Breathlessness was always a feature of disease and excess wheezing was present in 79% of patients. Fever (>38°C) was present in only 38.5%. Chest pain and haemoptysis were uncommon. Six out of 33 (18%) patients had tracheobronchitis observed during bronchoscopy. The median delay between symptoms and diagnosis was 8.5 days. The mortality rate was high: 53 out of 56 (95%) patients died despite invasive ventilation and antifungal treatment in 43 (77%) of them. In chronic obstructive pulmonary disease patients, invasive pulmonary aspergillosis currently carries a very poor prognosis. Outcome could perhaps be improved by more rapid diagnosis and prompt therapy with voriconazole.

Effect of dopamine on gastrointestinal motility during critical illness

Objective: To document the action of dopamine on gastrointestinal motility in mechanically ventilated patients. Design: Crossover, randomized, placebo-controlled study. Setting: General intensive care unit (ICU) in a university hospital. Patients: Twelve mechanically ventilated patients in a stable hemodynamic condition, with no contraindication to enteral feeding.¶Interventions: Dopamine (4 μg/kg per minute) and placebo were infused over 8 h (4 h fasting, followed immediately by 4 h nasogastric feeding at 100 kcal per hour) on two consecutive days, in a random order. Pressure changes in the gastric antrum (four sites) and in the duodenum (two sites) were recorded by perfused catheter manometry. Each session started with the institution of dopamine or placebo infusion.¶Measurements and results: The migrating motor complex and its three successive phases were identified (phase I, period of quiescence; phase II, period of irregular contractile activity; phase III or activity front, period of high-frequency, regular contractions). Contractions and activity fronts at each site were quantified during fasting and feeding. The mean duration of the fasting migrating motor complex was determined in the duodenum, as well as the contribution of each phase (phases I, II, III) to the length of the complete cycle. The propagation characteristics of each activity front were assessed visually. The number of contractions was lower in the antrum (p = 0.024) and phase III motor activity higher in the duodenum [incidence of activity fronts (p = 0.008); number of phase III contractions (p = 0.009)] during dopamine infusion than with placebo. These modifications observed under dopamine were related to decreased antral contractions during fasting (p = 0.050), increased incidence of activity fronts during feeding (p = 0.031), and increased number of phase III contractions during fasting (p = 0.037). In both groups (placebo and dopamine) activity fronts rarely started in the antrum, and abnormally propagated activity fronts were found in the duodenum in some patients. Conclusions: Low-dose dopamine adversely affects gastroduodenal motility in mechanically ventilated critically ill patients.

Gastric Acid and Pancreatic Polypeptide Responses to Sham Feeding Are Impaired in Diabetic Subjects with Autonomic Neuropathy

To assess the relationship between cardiac and extracardiac dysfunction in diabetic autonomic neuropathy, the gastric acid output and the pancreatic polypeptide (hPP) secretion in response to sham feeding were evaluated in diabetic patients with (group 1) and without (group 2) cardiac autonomic neuropathy (CAN), and in normal subjects (group 3). All patients assigned to the group with CAN exhibited an impaired beat-to-beat heart rate variation during deep breathing. The basal gastric acid output was comparable in the three groups (1.3 ± 0.5, 2.8 ± 1.5, and 3.9 ± 1.5 mmol/h, respectively). In contrast, the gastric acid output stimulated by sham feeding was significantly lower in patients with CAN (5.3 ±1.3 mmol/h) thanin diabetic subjects without CAN (14.0 ± 3.5 mmol/h; P < 0.01) and in controls (10.9 ± 3.1; P < 0.05). The maximal gastric acid secretion capacity, determined after pentagastrin injection, was similar in all patients. Mean basal hPP concentrations were comparable in the three groups (185 ± 53 pg/ml, 131 ± 29 pg/ml, and 116 ± 19 pg/ml). In the controls and diabetic subjects without CAN, a significant mean 60% increase of the hPP levels above basal values was observed during sham feeding. In contrast, no significant hPP response occurred in the group with CAN. These data suggest that diabetic CAN is associated with dysfunctions of the vagal pathways controlling the gastric acid output and the hPP secretion. Moreover, the results demonstrate a strong association between cardiac autonomic neuropathy and gastric vagal neuropathy (P < 0.001).

Combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients.

The aim of this study was to evaluate the safety and diagnostic yield of bedside bronchoalveolar lavage (BAL) combined with fibrescopic transbronchial lung biopsy (TBLB) in determining the aetiology of pulmonary infiltrates in mechanically ventilated patients. The records of 38 mechanically ventilated patients who underwent BAL/TBLB to investigate unexplained pulmonary infiltrates were retrospectively reviewed. Patients were divided into two groups: immunocompetent (group 1: n=22; group 1a: n=11, late acute respiratory distress syndrome (ARDS); group 1b: n=11, no ARDS) and immunocompromised (group 2, n=16). The procedure allowed a diagnosis in 28 patients (74%), inducing therapeutic modification in 24 (63%) and confirmation of clinical diagnosis in four (11%). In groups 1a, 1b and 2, diagnosis was obtained in 11 out of 11 (fibroproliferation), seven out of 11 and 10 out of 16 patients, and therapy changed in 11 out of 11 (administration of steroids), six out of 11 and seven out of 16 patients, respectively. Pneumothorax occurred in nine patients (four of group 1a), bleeding in four (<35 mL), and transient hypotension in two. No fatalities were procedure-related. Combined bronchoalveolar lavage/transbronchial lung biopsy is of diagnostic and therapeutic value in mechanically ventilated patients with unexplained pulmonary infiltrates, excluding those with late acute respiratory distress syndrome. Although complications are to be expected, the benefits of the procedure appear to exceed the risks in patients in whom a histological diagnosis is deemed necessary.

Duodenal motor response to continuous enteral feeding is impaired in mechanically ventilated critically ill patients.

In order to investigate the duodenal motor response to continuous enteral feeding during critical illness, we recorded the duodenal contractions of 12 mechanically ventilated critically ill patients during a 4 h fasting period immediately followed by another 4 h period of continuous (100 kcal/h) nasogastric feeding with a polymeric diet. Duodenal motility was recorded by manometry (perfused catheter technique) and the migrating motor complexes (MMC) were identified by their activity front (period of high frequency, regular contractions). The incidence and the mean duration of activity fronts as well as the mean duration of the MMC (time interval separating two successive activity fronts) recorded during both periods were compared. The incidence of activity fronts (fasting: median: 2.5, interquartile range: 5.5; feeding: median: 2, interquartile range: 3.5), their duration (fasting: 6.2 +/- 1.6 min; feeding: 5.8 +/- 1.6 min), and the mean duration of the MMC (fasting: 50.9 +/- 24.7 min; feeding: 49.1 +/- 20.3 min) were similar during both periods. We conclude that in these patients, the fasting pattern of motility is not interrupted by the continuous nasogastric administration of a polymeric diet. Since the activity fronts of the MMCs are highly propulsive, we suggest that their abnormal persistence during feeding may play a role in the pathophysiology of unexplained diarrhoea in some critically ill patients.

Another case of “European hantavirus pulmonary syndrome” with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Gastric acidity and duodenogastric reflux during nasojejunal tube feeding in mechanically ventilated patients

Objective: In order to prevent gastric microbial overgrowth, which may complicate nasogastric feeding, administration of nutrients more distally into the gut has been advocated in intensive care patients, as it offers the advantage of keeping the stomach empty and acid. In this study, we assessed the impact of jejunal feeding upon gastic pH in a group of mechanically ventilated, critically ill patients, with special focus on duodenogastric reflux as a possible cause of gastric alkalinization during jejunal nutrition. Design: Prospective experimental study. Setting: Multidisciplinary intensive care unit of a university hospital. Patients and methods: Gastric pH was recorded by continuous pHmetry over a 4-h period of fasting followed by a 4-h period of nasojejunal feeding at 100 kcal/h in 21 mechanically ventilated, critically ill patients. To determine the contribution of duodenogastric reflux to modifications of gastric acidity, the diet was traced with [111In] DTPA (pentetic acid) in 11 of these 21 patients; gastric contents were aspirated every 30 min, then analysed for measurement of radioactivity, glucose, and bile acid concentration. Measurements and results: Median intragastric pH increased slightly from 1.59 (1.20–2.73; interquartile range) (fasting) to 2.33 (1.65–4.64) (feeding) (p = 0.013), and the length of time that the pH was 4 or above increased from 1 (0–24) to 9 (0–142) min (p = 0.026). The variability of pH values and the number of acute alkalinization episodes did not change between the two phases. In 10 of 11 patients in which the diet was labeled with [111In] DTPA, reflux was documented at a given time of the feeding period. Bile acid concentrations in the stomach increased from 392 (61–1076) (fasting) to 1446 (320–2770) μmol/l (feeding) (p = 0.010) and mean glucose concentration increased from 59 (28–95) to 164 (104–449) mg/dl (p = 0.006). Conclusion: Duodenogastric reflux is common in mechanically ventilated critically ill patients with nasojejunal feeding tubes. It occurs both during fasting and during nasojejunal feeding. During nasojejunal feeding, moderate alkalinization of the gastric contents occurs as a result of bile and nutrient reflux.

Repetitive endoscopy and continuous alkaline gastric irrigation in a case of arsenic poisoning.

Background: The poor prognosis of patients with persistent gastrointestinal radio-opacities after oral arsenic poisoning supports efficient gastrointestinal decontamination as critical for survival. In a case of massive arsenic ingestion, we performed repetitive gastric endoscopy and a continuous alkaline irrigation of the stomach over several days.Case Report: A 41-year-old woman was admitted 4 hours after intentional ingestion of trivalent arsenic powder 5 g. The admission abdominal X-ray confirmed the presence of multiple gastric opacities. Initial treatment was gastric lavage with normal saline, dimercaprol chelation, and supportive therapy. Since gastric opacities persisted on the abdominal X-ray at 34 hours despite repeated gastric lavage, a gastroscopy was performed showing nonremovable agglomerates. In an attempt to achieve further gastric decontamination, we performed a continuous gastric alkaline irrigation. After 3 days of alkaline irrigation, the abdomen was normal on X-ray but the gastroscopy still showed arsenic concretions. Alkaline irrigation was continued for another 3 days until total disappearance of arsenic agglomerates at the gastroscopy. Admission urinary arsenic was 3663 μgmg/L. A total of 46.2-mg of inorganic arsenic, or less than 1% the ingested dose, was extracted from the stomach by this technique. The patient was discharged from the intensive care unit 20 days after admission without sequelae.

Reversible myocardial dysfunction in a patient with alcoholic ketoacidosis: A role for hypophosphatemia

A 39-year-old woman had alcoholic ketoacidosis complicated by reversible life-threatening myocardial dysfunction. This complication occurred a few hours after correction of acidosis in association with severe hypophosphatemia. A marked improvement in clinical, echocardiographic, and hemodynamic features was associated with the normalization of the serum phosphorus level. This case illustrates a rare complication of hypophosphatemia, emphasizing the need for emergency physicians to consider this metabolic disorder in the treatment of patients with alcoholic ketoacidosis. The pathogenesis of hypophosphatemia in alcoholic ketoacidosis, its potential role in myocardial dysfunction, and its therapeutic implications in emergencies are discussed.

Venovenous ECMO in life-threatening radiocontrast mediated-ARDS

Sir: Acute non-cardiogenic pulmonary edema is an uncommon complication of intravascular radiocontrast administration. All the cases previously described have recovered fully with conventional ventilatory support. We report a patient with lifethreatening radiocontrast mediated-acute respiratory distress syndrome (ARDS), who was successfully managed with aemergencyo venovenous extracorporeal membrane oxygenation (ECMO) because sufficient oxygenation could not be achieved by conventional ventilation alone. A 62-year-old man presented with ARDS 5 min after receiving low-osmolar ionic contrast media (140 ml of Hexabrix 200) for coronary angiogram. His respiratory rate was 35 breaths/min, blood pressure 60/40 mmHg and pulse rate 125/min. His PaO2 was 49 mmHg, PaCO2 50.4 mmHg and pH 7.18 (base excess: ±8.9) on 12 l/min O2 administered by a facemask. Mechanical ventilation was started with a FIO2 1.0, VT of 10 ml/kg, respiratory rate 14, positive end-expiratory pressure (PEEP) + 5 cm H2O and inspiratory/expiratory (I/E) ratio 1:1 with a peak inspiratory pressure (PIP) of 32 cm H2O. His mean pulmonary artery pressure was 21 mmHg (31/15), central venous pressure 9 mmHg, pulmonary capillary wedge pressure 10 mmHg and cardiac index 3.53 l/min per m2. Chest X-ray showed bilateral edema with normal cardiothoracic index. Laboratory investigations, electrocardiogram, echocardiography and the coronarography were normal. The protein concentration of pulmonary secretions collected through the endotracheal tube was 5.2 mg/dl whereas a simultaneously measured plasmatic protein level was 6.1 mg/dl. Three hours after admission, hypoxia (PaO2 45 mmHg, PaCO2 32 mmHg, pH 7.4) persisted despite the use of inverse I/E ratio (2/1), FIO2 1.0, PEEP of + 10 cm H2O, and PIP of 38 cm H2O. Neither NO titration (5, 10, 20 ppm) nor curarisation improved gas exchanges. His mean arterial pressure was maintained above 60 mmHg with difficulty (continuous infusion of vasopressive agents: epinephrine 0.3 mg/h, norepinephrine 20 mg/min, dopamine 3 mg/kg per min). In view of the life-threatening hypoxia, ECMO was initiated. Femoral and internal jugular veins were cannulated percutaneously and a venovenous blood flow of 4 l was obtained using a centrifugal pump (Centrimed, Sorin). A heparin-coated membrane oxygenator (Bentley, Baxter) was used with a membrane surface area 1.8 m2 and FIO2 1.0. Adequate gas exchanges were obtained (PaO2: 72 mmHg, PaCO2: 41 mmHg, pH: 7.34) and a spectacular improvement of the hemodynamic instability occurred (vasopressors were stopped within 18 h). Consecutively, the ventilatory support was reduced: respiratory rate 8/min, FIO2 0.7, PEEP + 5 cm H2O and PIP + 29 cm H2O. The patient was weaned from ECMO after 50 h and from mechanical ventilation 7 days after admission. Two weeks later, the patient was discharged without pulmonary symptoms. Only five reports of radiocontrast mediated-ARDS documented by a low pulmonary capillary wedge pressure have been described previously [1, 2]. In those cases, clinical improvement was seen in a few hours to several days with supportive therapy and conventional mechanical ventilation. Our patient had a life-threatening ARDS following radiocontrast injection. He was successfully managed by ECMO. We cannot exclude the possibilities that the improvement observed was induced by a spontaneous remission of the radiocontrast-mediated ARDS or that our patient could have been successfully treated with conventional ventilation by using different ventilator settings. However, this observation shows that intravenous radiocontrast material can induce life-threatening noncardiac pulmonary edema and that ECMO, although still controversial for adults [3], might be a useful tool for the emergency treatment of acute severe reversible hypoxemia [4, 5]. We think that the utility of ECMO in this context has to be investigated further.