Mariano Alberto Pennisi

A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome

Objective: In randomized studies of heterogeneous patients with hypoxemic acute respiratory failure, noninvasive positive pressure ventilation (NPPV) was associated with a significant reduction in endotracheal intubation. The role of NPPV in patients with acute respiratory distress syndrome (ARDS) is still unclear. The objective was to investigate the application of NPPV as a first‐line intervention in patients with early ARDS, describing what happens in everyday clinical practice in centers having expertise with NPPV. Design: Prospective, multiple‐center cohort study. Setting: Three European intensive care units having expertise with NPPV. Patients: Between March 2002 and April 2004, 479 patients with ARDS were admitted to the intensive care units. Three hundred and thirty‐two ARDS patients were already intubated, so 147 were eligible for the study. Interventions: Application of NPPV. Measurements and Main Results: NPPV improved gas exchange and avoided intubation in 79 patients (54%). Avoidance of intubation was associated with less ventilator‐associated pneumonia (2% vs. 20%; p < .001) and a lower intensive care unit mortality rate (6% vs. 53%; p < .001). Intubation was more likely in patients who were older (p = .02), had a higher Simplified Acute Physiology Score (SAPS) II (p < .001), or needed a higher level of positive end‐expiratory pressure (p = .03) and pressure support ventilation (p = .02). Only SAPS II >34 and a Pao2/Fio2 ≤175 after 1 hr of NPPV were independently associated with NPPV failure and need for endotracheal intubation. Conclusions: In expert centers, NPPV applied as first‐line intervention in ARDS avoided intubation in 54% of treated patients. A SAPS II >34 and the inability to improve Pao2/Fio2 after 1 hr of NPPV were predictors of failure.

New treatment of acute hypoxemic respiratory failure: Noninvasive pressure support ventilation delivered by helmet: A pilot controlled trial

OBJECTIVE To assess the efficacy of noninvasive pressure support ventilation (NPSV) using a new special helmet as first-line intervention to treat patients with hypoxemic acute respiratory failure (ARF), in comparison to NPSV using standard facial mask. DESIGN AND SETTING Prospective clinical pilot investigation with matched control group in three intensive care units of university hospitals. PATIENTS AND METHODS Thirty-three consecutive patients without chronic obstructive pulmonary disease and with hypoxemic ARF (defined as severe dyspnea at rest, respiratory rate >30 breaths/min, PaO2:FiO2 < 200, and active contraction of the accessory muscles of respiration) were enrolled. Each patient treated with NPSV by helmet was matched with two controls with ARF treated with NPSV via a facial mask, selected by simplified acute physiologic score II, age, PaO2/FiO2, and arterial pH at admission. Primary end points were the improvement of gas exchanges, the need for endotracheal intubation, and the complications related to NPSV. RESULTS The 33 patients and the 66 controls had similar characteristics at baseline. Both groups improved oxygenation after NPSV. Eight patients (24%) in the helmet group and 21 patients (32%) in the facial mask group (p = .3) failed NPSV and were intubated. No patients failed NPSV because of intolerance of the technique in the helmet group in comparison with 8 patients (38%) in the mask group (p = .047). Complications related to the technique (skin necrosis, gastric distension, and eye irritation) were fewer in the helmet group compared with the mask group (no patients vs. 14 patients (21%), p = .002). The helmet allowed the continuous application of NPSV for a longer period of time (p = .05). Length of stay in the intensive care unit, intensive care, and hospital mortality were not different. CONCLUSIONS NPSV by helmet successfully treated hypoxemic ARF, with better tolerance and fewer complications than facial mask NPSV.

Ketamine Increases Human Motor Cortex Excitability to Transcranial Magnetic Stimulation

Subanaesthetic doses of the N‐methyl‐d‐aspartate (NMDA) antagonist ketamine have been shown to determine a dual modulating effect on glutamatergic transmission in experimental animals, blocking NMDA receptor activity and enhancing non‐NMDA transmission through an increase in the release of endogenous glutamate. Little is known about the effects of ketamine on the excitability of the human central nervous system. The effects of subanaesthetic, graded incremental doses of ketamine (0.01, 0.02 and 0.04 mg kg−1 min−1, i.v.) on the excitability of cortical networks of the human motor cortex were examined with a range of transcranial magnetic and electric stimulation protocols in seven normal subjects. Administration of ketamine at increasing doses produced a progressive reduction in the mean resting motor threshold (RMT) (F(3, 18) = 22.33, P < 0.001) and active motor threshold (AMT) (F(3, 18) = 12.17, P < 0.001). Before ketamine administration, mean RMT ±s.d. was 49 ± 3.3 % of maximum stimulator output and at the highest infusion level it was 42.6 ± 2.6 % (P < 0.001). Before ketamine administration, AMT ±s.d. was 38 ± 3.3 % of maximum stimulator output and at the highest infusion level it was 33 ± 4.4 % (P < 0.002). Ketamine also led to an increase in the amplitude of EMG responses evoked by magnetic stimulation at rest; this increase was a function of ketamine dosage (F(3, 18) = 5.29, P= 0.009). In contrast to responses evoked by magnetic stimulation, responses evoked by electric stimulation were not modified by ketamine. The differential effect of ketamine on responses evoked by magnetic and electric stimulation demonstrates that subanaesthetic doses of ketamine enhance the recruitment of excitatory cortical networks in motor cortex. Transcranial magnetic stimulation produces a high‐frequency repetitive discharge of pyramidal neurones and for this reason probably depends mostly on short‐lasting AMPA transmission. An increase in this transmission might facilitate the repetitive discharge of pyramidal cells after transcranial magnetic stimulation which, in turn, results in larger motor responses and lower thresholds. We suggest that the enhancement of human motor cortex excitability to transcranial magnetic stimulation is the effect of an increase in glutamatergic transmission at non‐NMDA receptors similar to that described in experimental studies.

Noninvasive positive pressure ventilation using a helmet in patients with acute exacerbation of chronic obstructive pulmonary disease : a feasibility study

BackgroundNoninvasive positive pressure ventilation (NPPV) with a facemask (FM) is effective in patients with acute exacerbation of their chronic obstructive pulmonary disease. Whether it is feasible to treat these patients with NPPV delivered by a helmet is not known. MethodsOver a 4-month period, the authors studied 33 chronic obstructive pulmonary disease patients with acute exacerbation who were admitted to four intensive care units and treated with helmet NPPV. The patients were compared with 33 historical controls treated with FM NPPV, matched for simplified acute physiologic score (SAPS II), age, Paco2, pH, and Pao2:fractional inspired oxygen tension. The primary endpoints were the feasibility of the technique, improvement of gas exchange, and need for intubation. ResultsThe baseline characteristics of the two groups were similar. Ten patients in the helmet group and 14 in the FM group (P = 0.22) were intubated. In the helmet group, no patients were unable to tolerate NPPV, whereas five patients required intubation in the FM group (P = 0.047). After 1 h of treatment, both groups had a significant reduction of Paco2 with improvement of pH; Paco2 decreased less in the helmet group (P = 0.01). On discontinuing support, Paco2 was higher (P = 0.002) and pH lower (P = 0.02) in the helmet group than in the control group. One patient in the helmet group, and 12 in the FM group, developed complications related to NPPV (P < 0.001). Length of intensive care unit stay, intensive care unit, and hospital mortality were similar in both groups. ConclusionsHelmet NPPV is feasible and can be used to treat chronic obstructive pulmonary disease patients with acute exacerbation, but it does not improve carbon dioxide elimination as efficiently as does FM NPPV.

Early diagnosis of candidemia in intensive care unit patients with sepsis: a prospective comparison of (1→3)-β-D-glucan assay, Candida score, and colonization index

IntroductionThe culture-independent serum (1→3)-β-D-glucan (BG) detection test may allow early diagnosis of invasive fungal disease, but its clinical usefulness needs to be firmly established. A prospective single-center observational study was conducted to compare the diagnostic value of BG assay, Candida score (CS), and colonization index in intensive care unit (ICU) patients at risk for Candida sepsis.MethodsOf 377 patients, consecutively admitted to ICU for sepsis, 95 patients having an ICU stay of more than five days were studied. Blood specimens for fungal culture and BG measurement were obtained at the onset of clinical sepsis. For CS and colonization index calculations, surveillance cultures for Candida growth, and/or clinical data were recorded.ResultsSixteen (16.8%) patients were diagnosed with proven invasive fungal infection, 14 with candidiasis (13 candidemia and 1 mediastinitis) and 2 with pulmonary aspergillosis or fusariosis. Of 14 invasive Candida-infection patients, 13 had a serum sample positive for BG, 10 had a CS value ≥3, and 7 a colonization index ≥0.5. In the 12 candidemic patients, a positive BG result was obtained 24 to 72 hrs before a culture-documented diagnosis of invasive candidiasis. The positive and negative predictive values for the BG assay were higher than those of CS and colonization index (72.2% versus 57.1% and 27.3%; and 98.7% versus 97.2% and 91.7%, respectively).ConclusionsA single-point BG assay based on a blood sample drawn at the sepsis onset, alone or in combination withCS, may guide the decision to start antifungal therapy early in patients at risk for Candida infection.

A low-dose remifentanil infusion is well tolerated for sedation in mechanically ventilated, critically-ill patients

PurposeTo study the analgesic and sedative effects of remifentanil in critically-ill patients.MethodsRemifentanil infusion was started at 0.02 μg·kg−1·min−1 in ten mechanically ventilated critically-ill patients, and the infusion rate was increased to 0.05, 0.10, 0.15, 0.20, and 0.25 μg·kg−1·min−1 every 30 min. Basally and 25 min after each increase we measured: the Ramsey sedation score (RSS) and the respiratory response subscore of comfort scale (CSRR); the bispectral index (BIS) before and after lightly touching tracheal mucosa; heart rate and systemic arterial pressure; respiratory variables; plasma epinephrine and norepinephrine levels.ResultsInfusion rates up to 0.05 μg·kg−1·min−1 were effective against agitation and achieved a good degree of adaption to the respirator in all patients (RSS 2 or more and CSRR 3 or less); BIS decreased significantly; respiratory and circulatory variables were unaffected; mean plasma epinephrine levels decreased. At infusion rates higher than 0.05 μg·kg−1·min−1 RSS but not BIS decreased further and patient arousability caused by noxious stimuli was not prevented; respiratory drive suppression occurred at the infusion rates higher than 0.05 μg·kg−1·min−1 in four patients; bradycardia and arterial hypotension was observed in three patients; plasma epinephrine levels decreased significantly, while norepinephrine was unaffected; severe itching was experienced by one patient.ConclusionsLow doses of remifentanil (upto 0.05 μg·kg−1·min−1) can be useful in critically-ill patients in order to achieve calm and sedation. Higher doses can inhibit respiratory drive and require controlled mechanical ventilation.ZusammenfassungObjectifÉtudier les effets analgésiques et sédatifs du rémifentanil chez de grands malades.MéthodeUne perfusion de rémifentanil a été amorcée à 0,02 μg·kg−1·min−1 chez dix grands malades ventilés mécaniquement. La vitesse de perfusion a été augmentée à 0,05, 0,10, 0,15, 0,20 et 0,25 μg·kg−1·min−1 toutes les 30 min. Au début, et 25 min après chaque augmentation, nous avons mesuré : les scores de sédation de Ramsey (SSR) et le score auxiliaire de réponse respiratoire de l’échelle de confort (RREC); l’index bispectral (BIS) avant et après avoir légèrement stimulé la muqueuse trachéale; la fréquence cardiaque et la tension artérielle générale; les variables respiratoires; les niveaux plasmatiques d’adrénaline et de noradrénaline.RésultatsLes vitesses de perfusion allant jusqu’à 0,05 μg·kg−1·min−1 ont été efficaces contre l’agitation et ont permis une bonne adaptation au respirateur chez tous les patients (2 ou moins à SSR et 3 ou moins à RREC); le BIS a diminué de manière significative; les variables respiratoires et circulatoires n’ont pas été affectées; il y a eu une baisse des niveaux plasmatiques d’adrénaline et de noradrénaline. Sous des vitesses de perfusion plus élevées que 0,05 μg·kg−1·min−1, le SSR, mais non le BIS, a baissé davantage et la réaction des patients aux stimuli nuisibles n’a pu être empêchée; la suppression de la commande respiratoire s’est produite avec des perfusion audessus de 0,05 μg·kg−1·min−1 chez quatre patients; on a observé de la bradycardie et de l’hypotension chez trois patients; les niveaux plasmatiques d’adrénaline ont baissé significativement, mais ceux de la noradrénaline n’ont pas changé; un prurit sévère a été noté chez un patient.ConclusionDes doses faibles de rémifentanil (jusqu’à 0,05 μg·kg−1·min−1) peuvent apporter calme et sédation chez de grands malades. Des doses plus élevées peuvent inhiber la commande respiratoire et exiger une ventilation mécanique contrôlée.

Clinical review: Noninvasive ventilation in the clinical setting – experience from the past 10 years

This brief review analyses the progress of noninvasive ventilation (NIV) over the last decade. NIV has gained the dignity of first line intervention for acute exacerbation of chronic obstructive pulmonary disease, assuring reduction of the intubation rate, rate of infection and mortality. Despite positive results, NIV still remains controversial as a treatment for acute hypoxemic respiratory failure, largely due to the different pathophysiology of hypoxemia. The infection rate reduction effect achieved by NIV application is crucial for immunocompromised patients for whom the endotracheal intubation represents a high risk. Improvements in skills acquired with experience over time progressively allowed successful treatment of more severe patients.

Nonthyroidal Illness Syndrome and Prolonged Mechanical Ventilation in Patients Admitted to the ICU

BACKGROUND The effect of the nonthyroidal illness syndrome (NTIS) on the duration of mechanical ventilation (MV) has not been extensively investigated. This study aims to determine whether the NTIS is associated with the duration of MV in patients admitted to the ICU. METHODS We evaluated all patients admitted over a 6-year period to our ICU who underwent invasive MV and had measurement of serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) performed in the first 4 days after ICU admission and, subsequently, at least every 8 days during the time they received MV. The primary outcome measure was prolonged MV (PMV), which was defined as dependence on MV for > 13 days. RESULTS Two hundred sixty-four patients were included. Fifty-six patients (normal-hormone group) had normal thyroid function test results, whereas 208 patients (low-fT3 group) had, at least in one hormone dosage, low levels of fT3 with normal (n = 145)/low (n = 63) levels of fT4 and normal (n = 189)/low (n = 19) levels of TSH. Patients in the low-fT3 group showed significantly higher mortality and simplified acute physiology score II, and significantly longer duration of MV and ICU length of stay compared with the normal-hormone group. Two of the variables studied were associated with PMV, as follows: the NTIS (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.18 to 4.29; p = 0.01); and the presence of pneumonia (OR, 1.17; 95% CI, 1.06 to 3.01; p = 0.03). CONCLUSION The NTIS represents a risk factor for PMV in mechanically ventilated, critically ill patients.

Cerebral blood flow and metabolic changes produced by repetitive magnetic brain stimulation

Abstract We evaluated cerebral variation in oxyhemoglobin, deoxyhemoglobin, and cytochrome oxidase before and after transcranial magnetic and electrical stimulation in ten healthy volunteers using near-infrared spectroscopy. Immediately after magnetic but not after electric stimulation a significant increase in oxyhemoglobin and a decrease in cytochrome oxidase were observed (P < 0.05). Our data suggest that repetitive transcranial magnetic stimulation induces metabolic activation of the cerebral cortex together with an increase in cerebral blood flow.

The Role of Mannose-Binding Lectin in Severe Sepsis and Septic Shock

Severe sepsis and septic shock are a primary cause of death in patients in intensive care unit (ICU). Investigations upon genetic susceptibility profile to systemic complications during severe infections are a field of increasing scientific interest. Particularly when adaptive immune system is compromised or immature, innate immunity plays a key role in the immediate defense against invasive pathogens. Mannose-binding lectin (MBL) is a serum protein that recognizes a wide range of pathogenic microorganisms and activates complement cascade via the antibody-independent pathway. More than 30% of humans harbor mutations in MBL gene (MBL2) resulting in reduced plasmatic levels and activity. Increased risk of infection acquisition has been largely documented in MBL-deficient patients, but the real impact of this form of innate immunosuppression upon clinical outcome is not clear. In critically ill patients higher incidence and worse prognosis of severe sepsis/septic shock appear to be associated with low-producers haplotypes. However an excess of MBL activation might be also harmful due to the possibility of an unbalanced proinflammatory response and an additional host injury. Strategies of replacement therapies in critically ill patients with severe infections are under investigation but still far to be applied in clinical practice.