J. P. Cardinaud

Noninvasive Ventilation in Immunosuppressed Patients with Pulmonary Infiltrates, Fever, and Acute Respiratory Failure

BACKGROUND Avoiding intubation is a major goal in the management of respiratory failure, particularly in immunosuppressed patients. Nevertheless, there are only limited data on the efficacy of noninvasive ventilation in these high-risk patients. METHODS We conducted a prospective, randomized trial of intermittent noninvasive ventilation, as compared with standard treatment with supplemental oxygen and no ventilatory support, in 52 immunosuppressed patients with pulmonary infiltrates, fever, and an early stage of hypoxemic acute respiratory failure. Periods of noninvasive ventilation delivered through a face mask were alternated every three hours with periods of spontaneous breathing with supplemental oxygen. The ventilation periods lasted at least 45 minutes. Decisions to intubate were made according to standard, predetermined criteria. RESULTS The base-line characteristics of the two groups were similar; each group of 26 patients included 15 patients with hematologic cancer and neutropenia. Fewer patients in the noninvasive-ventilation group than in the standard-treatment group required endotracheal intubation (12 vs. 20, P=0.03), had serious complications (13 vs. 21, P=0.02), died in the intensive care unit (10 vs. 18, P=0.03), or died in the hospital (13 vs. 21, P=0.02). CONCLUSIONS In selected immunosuppressed patients with pneumonitis and acute respiratory failure, early initiation of noninvasive ventilation is associated with significant reductions in the rates of endotracheal intubation and serious complications and an improved likelihood of survival to hospital discharge.

Sequential use of noninvasive pressure support ventilation for acute exacerbations of COPD

Objectives: To compare the efficacy of noninvasive pressure support ventilation (NIPSV) in acute decompensation in chronic obstructive pulmonary disease (COPD) by means of a bi-level positive airway pressure support system (BiPAP) in a sequential mode with medical therapy alone; to assess the short-term physiologic effects of the device on gas exchange; and to compare patients successfully ventilated with NIPSV with those in whom NIPSV failed. Design: A prospective case series with historically matched control study. Setting: A general intensive care unit (ICU) of a university hospital. Patients: We evaluated the efficacy of administration of NIPSV in 42 COPD patients and compared this with standard treatment in 42 matched historical control COPD patients. Interventions: NIPSV was performed in a sequential mode, i. e., BiPAP in the spontaneous mode was used for at least 30 min every 3 h. Between periods of ventilation, patients could be systematically returned to BiPAP when the arterial oxygen saturation was < 0.85 or when the respiratory rate was > 30 breaths/min. Measurements and results: Success rate, mortality, duration of ventilatory assistance, and length of ICU stay were recorded. Eleven of the 42 patients (26 %) in the NIPSV group needed tracheal intubation compared with 30 of the 42 control patients (71 %). The 31 patients in whom NIPSV was successful were ventilated for a mean of 6 ± 3 days. In-hospital mortality was not significantly different in the treated versus the control group, but the duration of ventilatory assistance (7 ± 4 days vs 15 ± 10 days, p < 0.01) and the length of ICU stay (9 ± 4 days vs 21 ± 12, p < 0.01) were both shortened by NIPSV. BiPAP was effective in correcting gas exchange abnormalities. The pH values, measured after 45 min of BiPAP with optimal settings, in the success (7.38 ± 0.04) and failure (7.28 ± 0.04) patients were significantly different (p < 0.05). Conclusions: NIPSV, performed with a sequential mode, may be used in the management of patients with acute exacerbations of COPD.

Bronchoscopy with bronchoalveolar lavage via the laryngeal mask airway in high-risk hypoxemic immunosuppressed patients.

ObjectiveFiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) are major tools in the diagnosis of pulmonary complications in immunocompromised patients. Nevertheless, severe hypoxemia is an accepted contraindication to FOB in nonintubated patients. The purpose of this study was to evaluate the feasibility and safety of laryngeal mask airway (LMA)-supported FOB with BAL in immunosuppressed patients with suspected pneumonia and severe hypoxemia. DesignProspective, clinical investigation. SettingMedical intensive care unit of a university hospital. PatientsForty-six immunosuppressed patients admitted to our intensive care unit with suspected pneumonia and Pao2/Fio2 ≤ 125. InterventionsAfter the administration of 0.3 mg·kg−1 of etomidate, the patients were ventilated manually while receiving 1.0 Fio2. After the administration of 2.5 mg·kg−1 of propofol, followed by an infusion of 9.1 ± 2.3 mg·kg−1·hr−1of propofol, the LMA (size 3 or 4) was placed and connected to a bag-valve unit to allow manual ventilation with 1.0 Fio2. The FOB was introduced through a T-adapter attached to the LMA, and BAL was carried out with 150 mL of sterile 0.9% saline solution by sequential instillation and aspiration of 50-mL aliquots. Measurements and Main Results Three patients developed transient laryngospasm during passage of the bronchoscope via the LMA, which resolved with deepening of anesthesia. Changes in mean blood pressure, heart rate, Pao2/Fio2, and Paco2 values induced by the procedure did not reach significance. Seven patients (15%) presented hypotension (mean blood pressure, <60 mm Hg) maintained for 120 ± 40 secs, which required plasma expanders in three cases. Oxygen desaturation to <90% occurred in six patients (13%) during BAL. Nevertheless, the lowest Sao2 during the procedure was significantly higher than the initial Sao2 (94% ± 4% vs. 90% ± 2%). No patient required tracheal intubation during the 8 hrs after the procedure. BAL had an overall diagnostic yield of 65%. Because of the results obtained by using the BAL analysis, treatment was modified in 33 (72%) cases. ConclusionApplication of the LMA appears to be a safe and effective alternative to intubation for accomplishing FOB with BAL in immunosuppressed patients with suspected pneumonia and severe hypoxemia.

Fulminant Guillain-Barré syndrome mimicking cerebral death: case report and literature review.

Abstract A 45-year-old woman was admitted to the intensive care unit (ICU) for respiratory arrest. One day prior to admission, she had been nauseated and in a state of total exhaustion. On the night of admission she was unresponsive and developed gasping respiration. The patient was comatose with absent brainstem reflexes and appeared brain dead. Blood chemistry findings and brain magnetic resonance imaging were normal. Electroencephalogram revealed an alpha rhythmical activity unresponsive to painful or visual stimuli. The cerebrospinal fluid showed an albuminocytological dissociation. Guillain-Barré syndrome (GBS) was suspected. The electrophysiological evaluation revealed an inexcitability of all nerves. The pathological findings of the sural nerve biopsy indicated an axonal degeneration secondary to severe demyelination. GBS can very rarely present with coma and absent brainstem reflexes. This case illustrates the importance of electrophysiological tests and laboratory and imaging studies in patients with suspected brain death where a cause is not clearly determined.

Comparison of B-mode ultrasound and computed tomography in the diagnosis of maxillary sinusitis in mechanically ventilated patients.

ObjectiveTo compare B-mode ultrasound with sinus computed tomograph (CT) scan in the diagnosis of sinusitis in intubated patients undergoing mechanical ventilation. DesignProspective, clinical investigation. SettingMedical intensive care unit of a university hospital. PatientsFifty patients undergoing intubation and mechanical ventilation more than 2 days, with a clinical suspicion of paranasal sinusitis with purulent nasal discharge. InterventionsOne hundred paranasal sinuses were examined. A paranasal CT scan and a B-mode ultrasound were performed the same day. Radiologic maxillary sinusitis (RMS) was defined as complete opacification of the sinus or as the presence of an air-fluid level. Absence of RMS was defined as normal sinus or as the presence of mucosal thickening. Important RMS was defined by total opacity or air-fluid level larger than half of the sinus area. Moderate RMS was defined by air-fluid level inferior than half of the sinus area. For ultrasonographic procedure, the image defined as normal was an acoustic shadow arising from the front wall. Two levels of positive echography were described: 1) a moderate lesion was defined as the visualization only of the hyperechogenic posterior wall of the sinus; 2) an important lesion was defined as the hyperechogenic visualization of posterior wall and the extension by the internal wall of the sinus outlining the hypoechogenic sinus cavity. Measurements and Main Results Sensibility, specificity, positive predictive value, and negative predictive value of B-mode ultrasound compared with CT were, respectively: 100% (95% confidence intervals [95% CI] = 94.9–100.0), 96.7% (95% CI = 82.8–99.9), 98.6% (95% CI = 92.4–99.9), and 100% (95% CI = 88.1–100). The concordance between a moderate B-mode ultrasound lesion and a moderate RMS on CT, and between an important B-mode ultrasound lesion and an important RMS on CT, assessed using kappa statistics was 93%. The concordance between B-mode ultrasound’s results and CT’s results assessed using weighted kappa statistics was 97%. ConclusionB-mode ultrasound may be proposed first-line in a ventilated patient with suspicion of maxillary sinusitis.

Airway occlusion pressure at 0.1 s (P0.1) after extubation: an early indicator of postextubation hypercapnic respiratory insufficiency

Objective: To examine variables associated with postextubation respiratory distress in chronic obstructive pulmonary disease (COPD) patients. Design: Prospective, clinical investigation. Setting: Intensive care unit of a university hospital. Patients: Forty COPD patients, considered ready for extubation. Measurements and main results: We recorded, from the digital display of a standard ventilator, breathing frequency (f), tidal volume (VT) and f/VT for the respiratory pattern, airway occlusion pressure at 0.1 s (P0.1) for the respiratory drive and measured blood gases : i) before extubation, following 30 min of a 6 cm H2O pressure support (PS) ventilation trial, ii) 1 h after extubation, at the 30th min of a face mask 4 cm H2O PS ventilation trial. According to the weaning outcome, the patients were divided into two groups : respiratory distress, and non-respiratory distress within 72 h of the discontinuation of mechanical ventilation. The respiratory distress was defined as the combination of f more than 25 breaths/min, an increase in PaCO2 of at least 20 % compared with the value measured after extubation, and pH lower than 7.35. We determined whether those patients who developed respiratory distress after extubation differed from those who did not. Respiratory pattern data and arterial blood gases recorded, either before or after extubation, and P0.1 recorded before extubation, were inadequate to differentiate the two groups. Only P0.1 recorded 1 h after the discontinuation of mechanical ventilation differentiated the patients who developed respiratory distress from those who did not (4.2 ± 0.9 vs 1.8 ± 0.8, p < 0.01). Conclusions: P0.1 recorded after extubation may be a good indicator of postextubation respiratory distress. Measuring P0.1 and/or the analysis of the evolution of this parameter could facilitate decisions during the period following extubation.

ACUTE RESPIRATORY DISTRESS SYNDROME DUE TO ALL-TRANS RETINOIC ACID

Sir: We report a case of acute respiratory distress syndrome occurring during a treatment by all-trans retinoic acid. A 46-yearold non-smoking female presented with acute promyelocytic leukemia with classic translocation. The treatment began with all-trans retinoic acid orally at a daily dose of 45 mg/m2 body surface area. On day 16 after starting this treatment, she developed fever (39 °C), tachycardia (125 bpm), and dyspnea (respiratory rate: 28/min). Because of these symptoms, she was admitted to the Intensive Care Unit (ICU). A chest X-ray showed bilateral diffuse interstitial infiltrates without pleural effusion. An echocardiography revealed good left ventricular function without pericardial effusion. In order to diagnose infectious pneumonia, we performed a bronchoalveolar lavage (BAL) and empiric antimicrobial treatment was first begun with a combination of piperillin+tazobactam and vancomycin. All microbial samples failed to reveal the growth of pathogenic microorganisms. Histologic BAL fluid examination revealed an increased mature myeloid cells count with 60 % neutrophils and 5 % eosinophils. The blood leukocytes count had increased from 3.9 to 11 g/1. Blood gas analysis, with oxygen flow of 12 1/min, showed a PaO 2 of 59 mmHg. Four days later, her respiratory function deteriorated and required intermittent non-invasive ventilation with continuous positive airway pressure (8 cmH20 and FIO2:80 %). Alltrans retinoic acid was discontinued and she was treated with dexamethasone 10 mg intravenously every 12 h for six doses. Ten days later, all symptoms had disappeared and physical readings were normal. The use of all-trans retinoic acid induces hematologic remission in patients with acute promyelocytic leukemia [1]. The first complications of this treatment were reported by Huang and Castaigne [2, 3]. The retinoic acid syndrome involves hyperleukocytosis, fever, respiratory distress, pleural and pericardial effusion and hypotension occurring 2-21 days after the start of treatment with all-trans retinoic acid [4]. In our case, the symptoms were initially attributed to infectious pneumonia, because all the signs of retinoic acid syndrome were not present. Congestive heart failure did not seem likely since electrocardiograms and echocardiographs showed non-specific changes. After 4 days of ineffectiveness of the antibiotic therapy, we decided to begin corticosteroid treatment. Indeed, firstly, quantitative viral, bacterial and fungaI BAL fluid cultures revealed no growth; secondly, the histologic BAL fluid examination was compatible with retinoic acid syndrome and, thirdly, acute lung injury worsened, requiring non-invasive ventilation. Acute lung injury appears between 2-21 days of treatment with all-trans retinoic acid [5]. The diagnosis was difficult to establish because our patient developed respiratory failure only (neither shock nor renal failure). Even with sterile bacterial cultures, the diagnosis of infectious pneumonia is never completely excluded in cases of immunocompromised patients. In all reported cases, the symptoms were associated with a rising leucocyte count. The peak of the leucocyte count was not necessarily very high. The onset of respiratory distress was not associated with leukocytosis. Acute lung injury was almost certainly due to the increased migration of cells into the lung tissues. Retinoic acid upregulates genes that encode leukocyte adhesion receptors [6]. In this way, retinoic acid increases leukocyte adherence to capillary endothelial cells. This would explain the increased count of myeloid cells found in the BAL fluid. All-trans retinoic acid could increase integrin expression on the leukemic cell surface, which would enhance the cells adherence to capillary endothelium. Dexamethasone would block the capillaryleak syndrome, inhibit the generation of nitric oxide and secretion of pro-inflammatory cytokines. It is important to recognise this syndrome because intervention with dexamethasone may be life-saving.

Survival with extreme hypernatremia at 209 mmol/l

Sir: An 18-year-old female was admitted with corrosive stricture of the hypopharynx and proximal oesophagus. A transhiatal oesophagectomy and gastric pull-up was planned. A 16-G central venous cannula (Cavafix) was introduced into the right anticubital vein, but the brachial artery was punctured accidently. The cannula was removed and the punctured site pressed to achieve haemostasis. Soon after, the right hand became pale and cold, with absence of radial and ulnar artery pulsation and the pulse wave form fiom the saturation probe in the right hand disappeared. Doppler study of the right upper limb arteries showed narrowing of the puncture site and thrombus at the origin of the radial artery with sluggish flow density, so the diagnosis of arterial thrombosis and spasm was made. A stellate ganglion block on the right side was given with 15 ml 1.5 % lidocaine with adrenaline, following which the radial artery pulsations reappeared with an SpO 2 of 95 % in contrast to 99 % in the left hand. As the circulation in the right hand did not improve substantially despite repeated stellate ganglion blocks, an exploration of the radial artery was planned. Supraclavicular brachial plexus block was given with bupivacaine 0.5 % 30 ml, following which the radial pulse showed good volume and the SpO2 was equal in both limbs. The operation was deferred. Subsequently, the patient received multiple stellate ganglion blocks over the next few days with bupivacaine, following which her hand was warm with good capillary filling. She had an uneventful recovery and i year follow-up. Arterial cannulation for long periods has been associated with thrombosis [1] and ischaemic injury leading to amputation [2]. However, accidental, transient, single brachial artery puncture leading to such complications has so far not been reported. Bonica et al. [3] emphasized that brachial plexus block is useful in resolving the vascular spasm due to sympathetic stimulation, while repair or bypass surgery remains the main therapeutic modality. In this patient, the collateral circulation was probably inadequate, and repeated sympathetic blocks resulted in vasodilatation and improved perfusion of the right arm. Sympathetic block with stellate ganglion/brachial plexus block is a good precautionary measure to save the limb in such vascular injuries. Permanent ischaemic injury to the upper limb can be prevented by timely intervention with repeated stellate ganglion and brachial plexus blocks.

Severe noninfectious acute lung injury in early phase of bone marrow transplantation.

Sir: Bone marrow transplant recipients have a poor prognosis in intensive care units (ICUs), particularly in the early phase of transplantation. Several multifactorial etiologies may be responsible for respiratory failure, such as cardiogenic edema, infectious pneumonia, drug-related toxicity, alveolar hemorrhage, hematological malignancies, which may cause a relapse. The prognosis of this failure seems to be aggravated by the use of mechanical ventilation. Apart from the fact that these immunocompromised patients must have early intensive monitoring, perhaps with noninvasive ventilation, such as continuous positive airway pressure, the search for the cause of acute lung injury may be realized. Most respiratory failures occurring in the early phase of bone marrow transplantation are febrile. The first potentially treatable etiology is an infectious pneumonia. For this, the most efficient management is bronchoalveolar lavage (BAL) with viral, fungal, histological, and bacteriological examinations and quantitative cultures. Even if the discovery of the microorganism responsible for pneumonia seems to be less frequent in this group of patients and does not necessarily change the prognosis in the ICU, this search is in practice indispensable because of the possible institution of specific, appropriate treatment. In a lot of cases of marrow transplant recipients with febrile noncardiogenic respiratory failure, all microorganism typing is in vain. So the therapeutic dilemma is great, particularly when acute graft versus host disease (GVHD) or venoocclusive disease (VOD) is also suspected. Generally, most of these patients rapidly develop multiple organ failure syndrome. We reported our three-year experience of the clinical course of 24 allogeneic marrow transplant recipients (age 34 ± 8 years, Simplified Acute Physiology Score II 50 ± 10, leukocyte count 270 ± 240 g/l) who were admitted to the ICU with noncardiogenic febrile respiratory failure and no documentation of infection. The delay between ICU admission and engraftment was 11 ± 3 days, and at ICU admission, the arterial oxygen tension/fractional inspired oxygen ratio was 163 ± 57 and the lung injury score was 2.1 ± 0.56. All patients had a temporary weight gain, and pulmonary features were accompanied by confusion and liver and renal dysfunction in, respectively, 75, 96, and 71% of the patients. No patients developed septic shock. Four patients had cutaneous biopsy-proven diagnoses of GVHD and 2 patients had liver biopsy-proven diagnoses of VOD. GVHD and VOD were suspected in, respectively, 4 and 5 patients. In trying to determine the etiology of the pulmonary problems, there was no contribution from direct examination and culture of BAL fluid, which was performed in all patients. Mechanical ventilation was required in the 24 marrow transplant recipients. Eight patients with GVHD received intravenous corticosteroids (methylprednisolone 1±2 mg/kg per day in 6 patients and 5 and 7 mg/kg per day in 2 patients). Despite the negative microbial culture, all patients received empirical antibiotic therapy (betalactams, glycopeptide, amphotericin B). Altogether, 22/24 patients died of multiple organ failure. The two patients who survived had received high doses of glucocorticoids. In our experience, this group of marrow transplant recipients rapidly develop multiple organ failure after initial noncardiogenic acute lung injury. All of them had fever with no isolated microorganism. These multiple organ injuries have been linked to a generalized capillary leak syndrome [1]. Some authors have suggested that this endothelial damage was related to GVHD and other authors have shown that these complications were preceded by a release of tumor necrosis factor alpha and interleukin-2 [2, 3]. This phenomenon, which generally occurs in the engraftment period, must be related to circulating leukocytes [4]. In our study, high doses of methylprednisolone seemed to be efficacious in a small number of patients. Because of the possible proinflammatory pathogenesis of the capillary leak syndrome, anti-inflammatory treatment seems to be indicated in this type of complication of bone marrow engraftment [5]. It is true that we have no specific treatment of failures in the early phase of bone marrow transplantation. Despite the possible risk of corticoid therapy in the ICU, it may be necessary to try to stop unavoidable multiple organ dysfunction after initial respiratory failure in some marrow transplant recipients. Ongoing studies should clarify the role of mediators released by donor leukocyte cells in early noninfectious severe complications of allogeneic marrow transplantation.