Xenon pretreatment may prevent early memory decline after isoflurane anesthesia and surgery in mice.

Postoperative cognitive decline (POCD) is a common complication following surgery, but its aetiology remains unclear. We hypothesized that xenon pretreatment prevents POCD by suppressing the systemic inflammatory response or through an associated protective signaling pathway involving heat shock protein 72 (Hsp72) and PI3-kinase. Twenty-four hours after establishing long-term memory using fear conditioning training, C57BL/6 adult male mice (n = 12/group) received one of the following treatments: 1) no treatment group (control); 2) 1.8% isoflurane anesthesia; 3) 70% xenon anesthesia; 4) 1.8% isoflurane anesthesia with surgery of the right hind leg tibia that was pinned and fractured; or 5) pretreatment with 70% xenon for 20 minutes followed immediately by 1.8% isoflurane anesthesia with the surgery described above. Assessments of hippocampal-dependent memory were performed on days 1 and 7 after treatment. Hsp72 and PI3-kinase in hippocampus, and plasma IL-1ß, were measured using western blotting and ELISA respectively, from different cohorts on day 1 after surgery. Isoflurane induced memory deficit after surgery was attenuated by xenon pretreatment. Xenon pretreatment prevented the memory deficit typically seen on day 1 (P = 0.04) but not on day 7 (P = 0.69) after surgery under isoflurane anesthesia, when compared with animals that underwent surgery without pretreatment. Xenon pretreatment modulated the expression of Hsp72 (P = 0.054) but had no significant effect on PI3-kinase (P = 0.54), when compared to control. Xenon pretreatment also reduced the plasma level increase of IL-1ß induced by surgery (P = 0.028). Our data indicated that surgery and/or Isoflurane induced memory deficit was attenuated by xenon pretreatment. This was associated with a reduction in the plasma level of IL-1ß and an upregulation of Hsp72 in the hippocampus.

Acute inflammatory demyelinating polyneuropathy and a unilateral babinski/plantar reflex.

Acquired acute demyelinating peripheral polyneuropathy (AADP) is a general classification of pathologies that could affect secondary the peripheral nervous system. They are characterized by an autoimmune process directed towards myelin. Clinically they are characterized by progressive weakness and mild sensory changes. Acute inflammatory demyelinating polyneuropathy often is referred to as Guillain-Barré syndrome (GBS). GBS is the major cause of acute nontraumatic paralysis in healthy people and it is caused by autoimmune response to viral agents (influenza, coxsackie, Epstein-Barr virus, or cytomegalovirus) or bacterial infective organisms (Campylobacter jejuni, Mycoplasma pneumoniae). A detailed history, with symptoms of progressive usually bilateral weakness, hyporeflexia, with a typical demyelinating EMG pattern supports the diagnosis. Progressive affection of respiratory muscles and autonomic instability coupled with a protracted and unpredictable recovery normally results in the need for ICU management. We present a case report of a patient with a typical GBS presentation but with a unilateral upgoing plantar reflex (Babinski sign). A unifying diagnosis was made and based on a literature search in Pubmed appears to be the first described case of its kind.

Chest physiotherapy prolongs duration of ventilation in the critically ill ventilated for more than 48 hours.

OBJECTIVE: This study aimed to determine the impact of providing chest physiotherapy after routine clinical assessment on the duration of mechanical ventilation, outcome and intensive care length of stay. DESIGN AND SETTING: Single-centre, single-blind, prospective, randomised, controlled trial in a university hospital general intensive care unit. PATIENTS AND PARTICIPANTS: 180 patients requiring mechanical ventilation for more than 48 h. INTERVENTIONS: Patients randomly allocated, one group receiving physiotherapy as deemed appropriate by physiotherapists after routine daily assessments and another group acting as controls were limited to receiving decubitus care and tracheal suctioning. MEASUREMENTS AND RESULTS: Primary endpoints were initial time to become ventilator-free, secondary endpoints included intensive care unit (ICU) and hospital mortality and ICU length of stay. Kaplan-Meier analysis censored for death revealed a significant prolongation of median time to become ventilator-free among patients receiving physiotherapy (p=0.047). The time taken for 50% of patients (median time) to become ventilator-free was 15 and 11 days, respectively, for physiotherapy and control groups. There were no differences between groups in ICU or hospital mortality rates, or length of ICU stay. The number of patients needing re-ventilation for respiratory reasons was similar in both groups.

Systemic inflammatory response and progression to severe sepsis in critically ill infected patients.

RATIONALE: The systemic inflammatory response syndrome has low specificity to identify infected patients at risk of worsening to severe sepsis or shock. OBJECTIVE: To examine the incidence of and risk factors for worsening sepsis in infected patients. METHODS: A 1-year inception cohort study in 28 intensive care units of patients (n = 1,531) having a first episode of infection on admission or during the stay. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of progression to severe sepsis or shock was 20% and 24% at Days 10 and 30, respectively. Variables independently associated (hazard ratio [HR]) with worsening sepsis included: temperature higher than 38.2 degrees C (1.6), heart rate greater than 120/minute (1.3), systolic blood pressure higher than 110 mm Hg (1.5), platelets higher than 150 x 109/L (1.5), serum sodium higher than 145 mmol/L (1.5), bilirubin higher than 30 mumol/L (1.3), mechanical ventilation (1.5), and five variables characterizing infection (pneumonia [HR 1.5], peritonitis [1.5], primary bacteremia [1.8], and infection with gram-positive cocci [1.3] or aerobic gram-negative bacilli [1.4]). The 12 weighted variables were included in a score (Risk of Infection to Severe Sepsis and Shock Score, range 0-49), summarized in four classes of "low" (score 0-8) and "moderate" (8.5-16) risk (9% and 17% probability of worsening, respectively), and of "high" (16.5-24) and "very high" (score > 24) risk (31% and 55% probability, respectively). CONCLUSIONS: One of four patients presenting with infection/sepsis worsen to severe sepsis or shock. A score estimating this risk, using objectively defined criteria for systemic inflammatory response syndrome, could be used by physicians to stratify patients for clinical management and to test new interventions.

Antibiotic pharmacokinetic and pharmacodynamic considerations in critical illness.

BACKGROUND: Many factors over which there may be little control may influence the response of a patient to therapy. However, therapy with antibiotics can be readily optimised. DISCUSSION: Concentration-dependent agents such as aminoglycosides appear effective and to entail fewer side effects when given in large, infrequent doses. There is also evidence that time-dependent antibiotics often fail to reach adequate concentrations throughout the treatment period. To date no randomised controlled prospective trial has demonstrated improvement in clinical outcome following infusion rather than intermittent boluses of time-dependent antibiotics. Critical illness alters antibiotic pharmacokinetics principally through increases in volume of distribution. Other than glycopeptides and aminoglycosides, antibiotic blood concentrations are rarely monitored and therefore adequate concentrations can only be inferred from clinical response. CONCLUSIONS: Failure to respond within the first few days of empirical treatment may be due to antibiotic resistance or inadequate doses. Therefore the same rigor should be applied to achieving adequate antibiotic concentrations as is applied to inotropes, which are titrated to achieve predetermined physiological targets.

Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study.

OBJECTIVES: To examine the incidence of infections and to describe them and their outcome in intensive care unit (ICU) patients. DESIGN AND SETTING: International prospective cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge. PATIENTS: A total of 14,364 patients were admitted to the ICUs, 6011 of whom stayed less than 24 h and 8353 more than 24 h. RESULTS: Overall 3034 infectious episodes were recorded at ICU admission (crude incidence: 21.1%). In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes (crude incidence: 18.9%) including 713 (45%) in patients already infected at ICU admission. These rates varied between ICUs. Respiratory, digestive, urinary tracts, and primary bloodstream infections represented about 80% of all sites. Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections (71% and 86%, respectively vs. 55%). About 28% of infections were associated with sepsis, 24% with severe sepsis and 30% with septic shock, and 18% were not classified. Crude hospital mortality rates ranged from 16.9% in non-infected patients to 53.6% in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay. CONCLUSIONS: The crude incidence of ICU infections remains high, although the rate varies between ICUs and patient subsets, illustrating the added burden of nosocomial infections in the use of ICU resources.