Characteristics and outcome of patients with newly diagnosed advanced or metastatic lung cancer admitted to intensive care units (ICUs).

BACKGROUND: Although patients with advanced or metastatic lung cancer have poor prognosis, admission to the ICU for management of life-threatening complications has increased over the years. Patients with newly diagnosed lung cancer appear as good candidates for ICU admission, but more robust information to assist decisions is lacking. The aim of our study was to evaluate the prognosis of newly diagnosed unresectable lung cancer patients. METHODS: A retrospective multicentric study analyzed the outcome of patients admitted to the ICU with a newly diagnosed lung cancer (diagnosis within the month) between 2010 and 2013. RESULTS: Out of the 100 patients, 30 had small cell lung cancer (SCLC) and 70 had non-small cell lung cancer. (Thirty patients had already been treated with oncologic treatments.) Mechanical ventilation (MV) was performed for 81 patients. Seventeen patients received emergency chemotherapy during their ICU stay. ICU, hospital, 3- and 6-month mortality were, respectively, 47, 60, 67 and 71%. Hospital mortality was 60% when invasive MV was used alone, 71% when MV and vasopressors were needed and 83% when MV, vasopressors and hemodialysis were required. In multivariate analysis, hospital mortality was associated with metastatic disease (OR 4.22 [1.4-12.4]; p = 0.008), need for invasive MV (OR 4.20 [1.11-16.2]; p = 0.030), while chemotherapy in ICU was associated with survival (OR 0.23, [0.07-0.81]; p = 0.020). CONCLUSION: This study shows that ICU management can be appropriate for selected newly diagnosed patients with advanced lung cancer, and chemotherapy might improve outcome for patients with SCLC admitted for cancer-related complications. Nevertheless, tumors' characteristics, numbers and types of organ dysfunction should be taken into account in the decisional process before admitting these patients in ICU.

Intensive care in patients with lung cancer: a multinational study.

BACKGROUND: Detailed information about lung cancer patients requiring admission to intensive care units (ICUs) is mostly restricted to single-center studies. Our aim was to evaluate the clinical characteristics and outcomes of lung cancer patients admitted to ICUs. PATIENTS AND METHODS: Prospective multicenter study in 449 patients with lung cancer (small cell, n = 55; non-small cell, n = 394) admitted to 22 ICUs in six countries in Europe and South America during 2011. Multivariate Cox proportional hazards frailty models were built to identify characteristics associated with 30-day and 6-month mortality. RESULTS: Most of the patients (71%) had newly diagnosed cancer. Cancer-related complications occurred in 56% of patients; the most common was tumoral airway involvement (26%). Ventilatory support was required in 53% of patients. Overall hospital, 30-day, and 6-month mortality rates were 39%, 41%, and 55%, respectively. After adjustment for type of admission and early treatment-limitation decisions, determinants of mortality were organ dysfunction severity, poor performance status (PS), recurrent/progressive cancer, and cancer-related complications. Mortality rates were far lower in the patient subset with nonrecurrent/progressive cancer and a good PS, even those with sepsis, multiple organ dysfunctions, and need for ventilatory support. Mortality was also lower in high-volume centers. Poor PS predicted failure to receive the initially planned cancer treatment after hospital discharge. CONCLUSIONS: ICU admission was associated with meaningful survival in lung cancer patients with good PS and non-recurrent/progressive disease. Conversely, mortality rates were very high in patients not fit for anticancer treatment and poor PS. In this subgroup, palliative care may be the best option.

[Acute respiratory failure due to Gemcitabine-induced pulmonary toxicity]. / Pneumopathie d'hypersensibilité à la Gemcitabine s'accompagnant d'insuffisance respiratoire aiguë

Gemcitabine is a therapeutic agent that has been recently employed in the treatment of various cancers. Pulmonary toxicity has rarely been described. We report a case of a patient treated with Gemcitabine who developed acute respiratory symptoms related to a hypersensitivity pneumonia. Despite a severe clinical and radiological presentation, the outcome was favorable with corticosteroid treatment. In the event of respiratory symptoms in patients receiving Gemcitabine further investigations (chest X-ray, thorax CT-scan, bronchoalveolar lavage) are indicated. In view of the severity of pulmonary toxicity that can be caused by Gemcitabine, re-introduction of treatment is not recommended. We compare our case with other published cases of Gemcitabine-induced pulmonary toxicity.

Benefit of surgery after chemoradiotherapy in stage IIIB (T4 and/or N3) non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to evaluate postchemoradiotherapy surgery in stage IIIB non-small cell lung cancer. METHODS: Forty patients with stage IIIB non-small cell lung cancer were included in this phase II study. A preoperative diagnosis of stage IIIB cancer was based on mediastinoscopy or a thoracotomy in all patients. Induction treatment included two cycles of cisplatin (100 mg/m(2), day 1), 5-fluorouracil (1 g/m(2), days 1-3), and vinblastine (4 mg/m(2), day 1) combined with 42 Gy of hyperfractionated radiotherapy delivering 21 Gy in two sessions. Patients with a clinical response were offered surgery. RESULTS: The minimum follow-up for survivors was 48 months. Thirty patients had a T4 lesion and 18 had N3 disease. Twenty-nine patients (73%) had a clinical objective tumor response after induction treatment. These 29 patients underwent thoracotomy, and a complete resection was performed in 23 (58%). Two postoperative deaths occurred (7%). Four patients had a pathologic complete response at the time of surgery (10%). The 5-year survival is 19% for the overall population. When only patients who had persistent viable tumor cells at surgery are considered (n = 25), the 5-year survival is 28%. The 5-year survival is 42% for patients having no mediastinal lymph node involvement at the time of surgery and being treated with complete resection. CONCLUSION: This study shows that surgery, when feasible, is associated with a 28% long-term survival for patients in whom chemoradiotherapy alone fails to control disease.

Diagnosis of pulmonary embolism in patients with proximal deep vein thrombosis: specificity of symptoms and perfusion defects at baseline and during anticoagulant therapy.

To determine the specificity of pulmonary embolism (PE) symptoms and lung scan perfusion defects in patients with deep vein thrombosis (DVT), we analyzed data on 400 patients with phlebography-proven proximal DVT included in a prospective trial. As the incidence of PE during anticoagulant therapy was the main outcome measure of the trial, all patients underwent lung scanning and/or pulmonary angiography within 48 h of inclusion, and then whenever PE was suspected. Angiography was recommended in patients with nondiagnostic lung scan. At baseline, the presence or absence of PE could be ascertained in 350 patients (87.5%), and 197 (56%) had PE. Sensitivity and specificity of symptoms for PE were 74 and 67%, respectively. Among 37 patients with symptoms and nondiagnostic lung scan, only 8 (22%) had PE at angiography. During anticoagulant therapy (3 mo), there were 29 events suspicious for PE, mostly (53%) within 2 wk of inclusion. Repeated perfusion studies with comparison to baseline tests excluded PE in 21 cases. Cumulated 3-mo risks of suspected and confirmed on-treatment PE were 6.8% (95% CI, 5.4- 8.2%) and 2.0% (95% CI, 0.6-3.4%) respectively. Even in patients with known proximal DVT, PE symptoms are unspecific and careful imaging studies are needed for diagnosis, both at baseline and during anticoagulant therapy.

[Spontaneous gas gangrene of the pancreas caused by Clostridium perfringens]. / Gangrène gazeuse spontanée du pancréas due à Clostridium perfringens.

The case of a 60-year-old patient with acute biliary pancreatitis spontaneously infected by Clostridium perfringens is reported. On CT scan, all the pancreatic bed was filled by gas. The patient survived. Four cases have previously been published. Three were fatal and 2 occurred after a pancreatic biopsy. Complete gas gangrene of the pancreas is a severity criterion and suggests an infection by Clostridium perfringens.

Lung resection for recurrence after pneumonectomy for metastases.

Resection of pulmonary recurrences after pneumonectomy for metastases is exceptional. Nevertheless in carefully selected patients surgery on the residual lung might be successfully performed. From January 1987 to February 1996, 5 patients underwent metastasectomy on single lung after pneumonectomy performed for the same metastatic disease. There were 3 male and 2 female with a mean age of 38 years at the time of surgery on single lung. All patients had a FEV1 > 40%. One patient (n degree 1) had 2 consecutive operations (wedge resections) on the right lower lobe followed 17 months later by right inferior lobectomy for metastases of soft tissue sarcoma. Three patients had only an operation on the residual lung (patient n degree 2 had 2 wedge resections for carcinoma; patient n degree 3 had 7 wedge resections for carcinoma; patient n degree 4 had 6 wedge resections for osteogenic sarcoma). The last patient (n degree 5) had 2 wedge resections on the right upper lobe and a large wedge resection on the right lower lobe for metastases of malignant corticosurrenaloma using a cardiopulmonary femoro-femoral by-pass without cardiac arrest. She postoperatively developed a right lower lobe venous infarction treated subsequently with a completion right lower lobectomy. She died in the postoperative course from cardiorespiratory insufficiency. The other patients had an uneventful postoperative course. Two patients (n degree 2 and n degree 4) died of their disease 14 and 12 months respectively after the surgery on the residual lung; by contrast 2 patients (40%) (n degree 1 and n degree 3) are still alive without recurrences 36 and 27 months after the last resection. In selected patients aggressive surgery for metastases on the residual lung can be successfully performed but the benefits in terms of long-term disease-free survival remain to be determined.

Nosocomial meningitis caused by multiresistant enterococcus as a life-threatening complication of pelvic injury: case report.

Bacterial meningitis after pelvic trauma has never been described. We recently treated a patient who developed, during the course of his hospitalization, multiresistant enterococcal meningitis after severe pelvic injury, including a comminutive sacral fracture. Dural tear may have been the main factor leading to secondary infection of the cerebrospinal fluid. Treatment with intravenous continuous infusion of vancomycin plus rifampin, associated with closed subarachnoid drainage, resulted in a complete cure. Therapeutic cerebrospinal fluid levels of vancomycin were obtained only during the first 8 days of treatment. Use of glycopeptides in meningitis and the role of cerebrospinal fluid drainage are discussed. Physicians should be aware of the diagnosis and therapeutic features of this life-threatening complication.

Thrombolysis for life-threatening pulmonary embolism 2 days after lung resection.

Early postoperative severe pulmonary embolism is usually considered an indication for surgical embolectomy because thrombolytic agents cannot be used. Severe pulmonary embolism was diagnosed 2 days after lung resection in two patients, including one with hypercapnia during spontaneous breathing, perhaps a unique feature of massive embolism on a single lung. Although emergency surgical embolectomy was available, both patients were given a bolus infusion of thrombolytic agents, with an immediate (within 1 h) clinical and hemodynamic improvement and a favorable outcome despite delayed major bleeding in one patient. The reported data and an analysis of the available literature support the view that recent surgery should be considered a relative rather than absolute contraindication to thrombolysis and that decision making in this setting should be based on a careful case-by-case evaluation of the expected benefits and risks of the various available treatments.

Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients.

Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.

Procedures for the diagnosis of pneumonia in ICU patients.

The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation. An important advance has been the development of the protected specimen brush technique. Secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia. However, this procedure has important limitations in that results are not available immediately, and in that a few false negative of false positive results may occur. Bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, because the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture. Microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for the early and rapid diagnosis of pneumonia in this setting. The lavage technique can also be conveniently incorporated into a protocol along with quantitative culture of samples obtained using the protected specimen brush. This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in most patients with pneumonia.

Evaluation of pulsed Doppler common carotid blood flow as a noninvasive method for brain death diagnosis: a prospective study.

Among the main causes for the relatively small number of organ donors, the delay in the diagnosis of brain death plays a major role. This prospective study was designed to evaluate whether pulsed Doppler mean and phasic common carotid blood flow (CCBF) combined with arterial and jugular venous blood gases could rapidly and specifically establish a diagnosis of brain death. CCBF was measured by an 8 MHz pulsed Doppler flowmeter, allowing measurement of the vessel diameter via a double transducer probe, which fixed the ultrasonic incidence angle. From an initial series of patients (n = 28) with an established diagnosis [brain death n = 14; severe coma with a Glasgow Coma Scale (GCS) less than 7, n = 14], the results of the logistic regression analysis process yielded the most discriminating parameters for brain death diagnosis: end-diastolic velocity (Ved - 1.4 vs. 12.7 cm/s; t = 7.67, P = 0.001) and blood flow (Qed - 13.6 vs. 121.4 ml/min). These parameters were then tested in a blind fashion on a second series of 28 comatose patients (GCS = 7). They resulted in correct diagnosis (brain death n = 14 or severe coma n = 14) for all patients. Brain death diagnosis was confirmed by clinical signs, EEG, and/or angiography. From the analysis of the overall population (n = 56), a value of Qed of less than 31.4 ml/mn indictes brain death. The authors conclude, that pulsed Doppler measurements of CCBF represent an early, low cost and noninvasive technique, the results of which may prompt legally accepted procedures, which in turn would reduce the delay required before brain death is diagnosed. Moreover, this technique could help in deciding on discontinuation of active therapy in severely injured patients.

[Calcium inhibitors: effects on cerebral blood flow and intracranial pressure]. / Anti-calciques: effets sur le débit sanguin cérébral et sur la pression intracrânienne.

Calcium entry blockers (CEB) have been a major advance in pharmacologic research in the last decade, especially in cardiovascular diseases. In neurology and intensive care, prescription of CEB seems to be more selective. CEB are potent cerebrovascular vasodilating drugs especially after KCL induced vasoconstriction. This property appears less evident when vasoconstriction is achieved by agonist substances. CEB act selectively on cerebral vessels, an effect which prevents the occurrence of systemic arterial hypotension. However they greatly modify the cerebrovascular response to arterial CO2. Concerning the cerebrovascular response to arterial CO2. Concerning their potential benefits in brain ischemia, it is now well admitted that CEB are useful in subarachnoid hemorrhage. Several controlled and uncontrolled human studies have demonstrated the CEB potency in vasospasm prevention and in cerebral ischemic consequences. Nonetheless when the vasospasm is installed, the benefit of the CEB appears less evident. In focal cerebral ischemia, data are few and unclear suggesting a cautious prescription of CEB. Finally CEB seem to increase intracranial pressure in humans, although this effect depends on the underlying neurologic pathology.

[Feasibility of calcium inhibitors in the treatment of brain disease following cardiac arrest]. / Possibilités des inhibiteurs calciques dans le traitement de l'encéphalopathie post-arrêt circulatoire.

One of the crucial factors affecting mortality and morbidity after circulatory arrest the ischemic neuronal damage following complete cessation of cerebral blood-flow. To date, no accepted pharmacologic neuroprotective therapy has emerged. Cerebral ischemia causes a rapid shift of Ca++ from the extracellular spaces into cells and it is assumed that this excessive entry of Ca++ is the final pathway of cell death. In addition, Ca++ is involved in the diffuse vasospasm which occurs after global cerebral ischemia. Therefore, calcium entry blockers such as dihydropyridines derivatives have sparked considerable interest especially because of their preferential cerebrovasodilating effects. In vivo studies have demonstrated protection from brain ischemia with calcium entry blockers. However no direct protective effect of these drugs has been shown on neurons. More recent results have underscored the importance of excitatory amino acid neurotransmitters and receptors (particularly N-Methyl-D-Aspartate receptors) in causing intracellular calcium overload and neuronal death after ischemia. Blockade of these receptors or their associated channels may be an interesting way to protect the brain against ischemic damage.

[Criteria for brain death: cessation of cerebral circulation demonstrated by Doppler ultrasonography of the carotid arteries]. / A propos des critères de la mort cérébrale: l'arrêt de la circulation cérébrale mis en évidence par le Döppler carotidien.

If human death is defined by brain death, its diagnosis needs medicolegal criteria based on clinical examination and EEG. However, this evaluation could be difficult because technical or physiological limitations might impair the interpretation, especially after barbiturates and/or hypothermia. Since brain death is characterized by an intracranial circulatory arrest, methods assessing this phenomenon are warranted. Among these methods, conventional or isotopic cerebral angiography appears the most promising, but it cannot be easily performed everywhere. Because superficial blood flow in arteries is now accurately measured by the pulsed Döppler technique, this prompted us to test the specificity and sensitivity of common carotid blood flow data for brain death diagnosis. Two series of age-matched patients (36 yrs in mean) were studied. Series 1 (n = 28) was used to define the discriminant parameters between 14 severe coma patients and 14 brain-dead patients diagnosed by the classical criteria. Then these parameters were prospectively tested in a blind manner on a second series of 28 patients suffering from severe coma. The parameters allowing us to classify patients as brain dead or not with a 100% specificity and sensitivity were: end diastolic blood flow (QED in ml/min), end diastolic blood flow velocity (VED), and cerebral metabolic index (CMI = QED x AV D 02). The most powerful discriminant parameter was QED, allowing a strictly non-invasive diagnosis of brain death.

[Surgically treated syphilitic gumma of the brain. Computerized tomography findings]. / Gomme syphilitique cérébrale opérée. Données du scanner X.

Syphilitic gumma is now exceptional. Symptomatology is non-specific and frequently, as in the case reported here, the onset is marked by a localized or generalized convulsion. A space-occupying lesion is recognized by angiography and CT. The precise diagnosis is suggested by evidence of arteritis or of a hypodense mass outlined by contrast or slight calcifications and confirmed by positive serology in a patient with a suspected cerebral tumor. In some cases a positive diagnosis can be made only by pathological examination after surgical ablation of the gumma. An area of central necrosis is surrounded by a granulomatous layer rich in plasmocytes (the polyclonal nature of the secretion is shown by immunocytochemistry) and a peripheral fibroblastic zone. The arteries are ensheathed by a dense inflammatory infiltrate constituted almost entirely by plasmocytes and their lumens are either stenosed or filled with endarteritic debris. Surgical treatment should be combined with penicillin administration. For a patient in good general condition with a suspected gumma, medical treatment can be given initially, with follow-up by CT, neurosurgery being indicated only in case of failure of medical therapy. The rarity of gummata in relation to other tertiary syphilitic lesions remains unexplained. The patient reported here had multiple infections including one due to cytomegalovirus after ablation of the gumma, highly suggesting an immunity disorder.