ABSTRACT
BACKGROUND: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. METHODS: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. RESULTS: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). CONCLUSION: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.
Subject(s)
Antibodies, Monoclonal, Humanized , Coronavirus Infections , Pandemics , Pneumonia, Viral , Receptors, Interleukin-6/antagonists & inhibitors , Respiration, Artificial/methods , Respiratory Insufficiency , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antiviral Agents/adverse effects , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Fever/diagnosis , Fever/drug therapy , Humans , Italy/epidemiology , Lymphocyte Count/methods , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2ABSTRACT
Both the steep head-down position and pneumoperitoneum increase the intracranial pressure (ICP), and their combination for a prolonged period during laparoscopic radical prostatectomy (LRP) might influence the central nervous system homeostasis. Changes in optic nerve sheath diameter (ONSD) may reflect those in ICP. This study aims to quantify the change in ONSD in response to peritoneal CO2 insufflation and steep Trendelenburg position during LRP. ONSD was measured by ultrasound in 20 patients undergoing LRP and ten awake healthy volunteers. In patients, ONSD was assessed at baseline immediately after induction of general anesthesia in supine position, 10 and 60 min from baseline in a 25° head-down position during pneumoperitoneum, and after deflation of pneumoperitoneum with the patient supine at 0° angle. ONSD in controls was assessed at baseline with the patient lying supine, after 10 and 60 min of 25° head-down position, and 10 min after repositioning at 0° angle. ONSD increased significantly in both patients and controls (p < 0.0001) without between-group differences. The mean increase was 10.3% (95% CI 7.7-12.9%) in patients versus 7.5% (95% CI 2.5-12.6%) in controls (p = 0.28), and didn't affect the time to recovery from anesthesia. In the studied patients, with a limited increase of end-tidal CO2 and airway pressure, and low volume fluid infusion, the maximal ONSD was always below the cut-off value suspect for increased ICP. ONSD reflects the changes in hydrostatic pressure in response to steep Trendelenburg position, and its increase might be minimized by careful handling of general anesthesia.
Subject(s)
Intracranial Hypertension , Laparoscopy , Head-Down Tilt , Humans , Intracranial Pressure , Male , Optic Nerve/diagnostic imagingABSTRACT
BACKGROUND: Severe imported Plasmodium falciparum malaria is a potentially life-threatening disease with a reported mortality rate of 5-10% when patients are admitted to the Intensive Care Unit. METHODS: To retrospectively review the clinical aspects, the value of severity predictive scores and the management of patients with severe P. falciparum malaria admitted to an ICU in Milano, Italy between January 2010 and December 2015. RESULTS: Twelve patients were included: seven were male and five female with a median age of 43 years. All were initially treated with intravenous quinine. Median parasitaemia upon admission was 14,5% (range 1-20%). At the time of ICU admission, 3 patients (25%) had 5 or more World Health Organization criteria for severe malaria while another 6 of them developed one or more of the latter during their stay in ICU. Five required mechanical ventilation because of respiratory failure due to ARDS. Four patients required renal replacement therapy. Three patients underwent blood exchange transfusion. All patients survived. CONCLUSIONS: Our retrospective evaluation of adults patients admitted to the ICU with severe imported P. falciparum malaria demonstrated a favourable outcome. Severity predictive scores currently in use probably overestimate the risk of malaria mortality in patients treated in health care systems of high income countries.