Ilias Andrianakis

Prevention of infection in multiple trauma patients by high-dose intravenous immunoglobulins

Objective: To investigate the activity of intravenous immunoglobulin (IVIG) as a prophylactic agent against infection in trauma victims. Design: Prospective, randomized, double‐blind, placebo‐controlled study. Setting: A 20‐bed university intensive care unit. Patients: Thirty‐nine trauma patients with injury severity scores (ISSs) of 16‐50. Interventions: Penicillin was given at the time of admission and continued at least until day 4. Twenty‐one patients received IVIG and 18 patients received human albumin at 1 g/kg in four divided doses (days 1, 2, 3, and 6). The two groups had similarities in age, gender, Acute Physiology and Chronic Health Evaluation II score, risk of death, and Glasgow Coma Scale score, but differing ISSs (p = .02), at the time of admission. Blood was collected on days 1, 4, and 7. Measurements and Main Results: Clinical variables related to infection were recorded. The complement components C3c, C4 and CH50, IgG, and the fractions of IgG were measured. The serum bactericidal activity (SBA) was assessed at 37°C (98.6°F) and 40°C (104.0°F) at the time of admission and during the course of IVIG administration. Controlling for ISS, IVIG‐treated patients had fewer pneumonias (p = .003) and total non‐catheter‐related infections (p = .04). Catheter‐related infections (p = .76), length of stay in the intensive care unit, antibiotic days, and infection‐related mortality did not differ between the two groups. A significantly increased trend in IgG and its subclasses was shown on days 4 and 7 in the IVIG group but not in the control group (p < .000001). No important differences were noted in complement fractions. The SBA of the groups was similar on day 1, but significantly higher on days 4 and 7 (p < .000001) in the IVIG group, remaining so controlling for complement and ISS. SBA was higher at 40°C (104.0°F) compared with 37°C (98.6°F) (p < .0001) under all three conditions. In both groups, low SBA (on days 1, 4, and 7) was associated with increased risk of pneumonia (p < .01) and non‐catheter‐related infections (p = .06 for day 1; p < .01 for days 4 and 7). Conclusions: Trauma patients receiving high doses of IVIG exhibit a reduction of septic complications and an improvement of SBA. Early SBA measurement may represent an index of susceptibility to infection.

Outcome in 1,000 head injury hospital admissions: the Athens head trauma registry

BACKGROUND The aim of this study was to establish a head trauma registry to (a) examine demographics, etiology, severity, clinical course, and outcome; (b) compare results with previous published series; (c) identify causes of bad outcomes; and (d) propose methods to improve therapy and prognosis. METHODS The following data were collected on 1,000 consecutive victims with head injury over 14 years of age admitted during a 4-year period: demographic characteristics, cause of injury, clinical variables, neuroimaging, therapy data, and outcome in 6 months. RESULTS Seventy-four percent were men, and mean age was 43 years. Seventy-one percent suffered injuries due to road crashes, 14% due to alcohol, and 2% due to substances. The secondary transfer rate was 49%. For severe injuries, the time intervals from incident to hospital and subsequently to neurosurgical unit were 35 minutes and 4 hours, respectively. In 65% and 72% of cases, there was no record of preresuscitation hypoxia or hypotension, respectively, whereas suspected or definite episodes of hypoxia and hypotension were 27% and 13%, respectively. Most cases were mild trauma (63%), the remaining were severe (26%) and moderate (11%) injuries. Severe systemic trauma coexisted in 18%. Cranial surgery rate was 19% and it increased to 39% in severe trauma. The 6-month overall good outcome was 71%, with lower rates in moderate (58%) and severe (24%) injuries. CONCLUSIONS The organization of Greeces first head injury registry offered an important preliminary core data concerning brain trauma etiology, management, and long-term outcome.

The level of hypotension during hemorrhagic shock is a major determinant of the post-resuscitation systemic inflammatory response: an experimental study

BackgroundTo evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.MethodsFifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringers lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).ResultsSerum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.ConclusionThe level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.

Cardiac arrest provoked by itraconazole and amiodarone interaction: a case report

IntroductionAzoles, and specifically itraconazole, are often prescribed for the treatment of fungal diseases or empirically for persistent sepsis in patients who are neutropenic or in intensive care. Occasional cardiovascular adverse events have been associated with itraconazole use, and are usually attributed to the interaction of itraconazole with cisapride, terfenadine or digoxin. Its interaction with amiodarone has not been previously described.Case presentationA 65-year-old Caucasian man was admitted to the Intensive Care Unit at our facility for an extensive ischemic stroke associated with atrial fibrillation. Due to rapid ventricular response he was started on intravenous amiodarone and few days later itraconazole was also prescribed for presumed candidemia. After receiving the first dose our patient became profoundly hypotensive but responded rapidly to fluids and adrenaline. Then, two months later, itraconazole was again prescribed for confirmed fungemia. After receiving the first dose via a central venous catheter our patient became hypotensive and subsequently arrested. He was resuscitated successfully, and as no other cause was identified the arrest was attributed to septic shock and his antifungal treatment was changed to caspofungin. When sensitivity test results became available, antifungal treatment was down-staged to itraconazole and immediately after drug administration our patient suffered another arrest and was once again resuscitated successfully. This time the arrest was related to itraconazole, which was discontinued, and from then on our patient remained stable until his discharge to our neurology ward.ConclusionsItraconazole and amiodarone coadministration can lead to serious cardiovascular adverse events in patients who are critically ill. Intensivists, pharmacists and medical physicians should be aware of the interaction of these two commonly used drugs.

Hypoxemic resuscitation from hemorrhagic shock prevents lung injury and attenuates oxidative response and IL-8 overexpression

We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.

Life-threatening bilateral empyema and mediastinitis complicating infectious mononucleosis

Abstract. Infectious mononucleosis, most commonly caused by Epstein-Barr virus (EBV), generally results in mild, self-limited illness characterized by fever, pharyngitis and lymphadenopathy. The young woman presented in our case report had clinical and serologic evidence of infectious mononucleosis and developed cervical abscess, which directly extended into the retropharyngeal space, mediastinum and the pleural spaces without lung involvement. After antibiotic and extensive surgical treatment she made a full recovery.

Brain eigenfrequency shifting as a sensitive index of cerebral compliance in an experimental model of epidural hematoma in the rabbit : Preliminary study

OBJECTIVE To verify brain eigenfrequency shifting after the occurrence of a lesion producing mass effect into the cranial vault. DESIGN Experimental animal study. SETTING Laboratory of experimental surgery affiliated with a university critical care department. SUBJECTS Six adult male New Zealand white rabbits. INTERVENTIONS A Camino ICP monitor was placed in the parenchyma, and a 5-Fr balloon-tipped catheter and accelerometer were placed into the epidural space. MEASUREMENTS Before and after the introduction of successive 0.1-mL increments of autologous blood into the balloon, intracranial pressure (ICP) was recorded along with the accelerometer signal obtained during free vibration of the skull triggered by a calibrated hammer. Fast Fourier transformation of the digitized signal provided the eigenfrequency spectrum. The eigenfrequency showing the sharpest decrease after the initial 0.1-mL volume addition was considered as the best frequency, and its variation in response to subsequent 0.1-mL increments represents the brain eigenfrequency shifting. MAIN RESULTS Brain eigenfrequency shifting to lower values occurs for small blood volume increments (up to 0.2 mL). When volume addition becomes >0.3 mL, brain eigenfrequency shifting to higher values is exhibited. The decrease in best frequency after the initial introduction of 0.1 mL is statistically significant (p = .003), in a range of volume in which no significant intracranial pressure difference appears. The respective variation of ICP is explained using a quadratic curve. For volumes of 0 to 0.1 mL, the change in ICP is not statistically significant (p = .08). CONCLUSIONS Changes of the brains physical characteristics by mass addition in the cranial vault can be expressed by brain eigenfrequency shifting. The method seems advantageous because it reliably detects mass additions at low levels where no ICP change occurs. Additionally, it provides serial measurements, and it is less invasive than the currently used methods for intracranial compliance.

Monocytes as a site of production of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the septic host.

The role of blood monocytes in the secretion of soluble triggering receptor expressed on myeloiod cells (sTREM-1) was studied in 90 patients with septic syndrome due to ventilator-associated pneumonia. Blood monocytes were isolated on 7 consecutive d after initiation of symptoms. Monocytes were incubated in the absence or presence of LPS and concentrations of sTREM-1 and TNFα in cell supernatants and serum were estimated by an enzyme-immunoassay. sTREM-1 and TNFα were consistently present at detectable levels in the cell supernatants. LPS induced increased levels of TNFα but not of sTREM-1. Supernatants recovered from monocytes on d 1 showed levels of sTREM-1 higher than those recovered on any of the following 6 d (p<0.05); these levels were higher in non-survivors than in survivors. Supernatants recovered from monocytes on d 1 of patients with severe sepsis had elevated concentrations of sTREM-1 compared to patients with septic shock and similar to patients with sepsis. A negative correlation was found between levels of sTREM-1 in the cell supernatants and the percentage of apoptotic monocytes. In essence, the above results suggest that monocytes contribute to the production of sTREM-1 in the event of septic syndrome.

Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation

Purpose Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury. Methods Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO2 = 95–105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO2 = 35–40 mmHg) followed, modifying the FiO2. Animals not subjected to shock constituted the sham group (n = 11, PaO2 = 95–105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed. Results Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor - alpha, interleukin (IL) -1β and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals. Conclusions Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory response and oxidative and nitrosative stresses.

Mediastinal Mass with Dysphagia in an Elderly Patient

Abstract.We report the use of endoscopic techniques for successful diagnosis in a case of atypical esophageal tuberculosis. Tuberculosis of the esophagus is an unusual presentation of this disease, having been estimated to occur in 0.15% of the people who die of tuberculosis. A few cases of possible primary tuberculous esophagitis have been described. This report describes a patient with dysphagia who appeared to have esophageal tuberculosis without HIV and in the absence of other signs of tuberculosis. The patient responded promptly to treatment with tuberculostatics.