Maurice Lamy

Cytokine serum level during severe sepsis in human IL-6 as a marker of severity

Forty critically ill surgical patients with documented infections were studied during their stay in an intensive care unit. Among these patients, 19 developed septic shock and 16 died, 9 of them from septic shock. Interleukin 1 beta (IL-1 beta), tumor necrosis factor (TNF alpha), and interleukin 6 (IL-6) were measured each day and every 1 or 2 hours when septic shock occurred. Although IL-1 beta was never found, TNF alpha was most often observed in the serum at a level under 100 pg/mL except during septic shock. During these acute episodes TNF alpha level reached several hundred pg/mL, but only for a few hours. In contrast, IL-6 was always increased in the serum of acutely ill patients (peak to 500,000 pg/mL). There was a direct correlation between IL-6 peak serum level and TNF alpha peak serum level during septic shock and between IL-6 serum level and temperature or C-reactive protein serum level. Moreover, IL-6 correlated well with APACHE II score, and the mortality rate increased significantly in the group of patients who presented with IL-6 serum level above 1000 pg/mL. Thus, IL-6 appears to be a good marker of severity during bacterial infection.

Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans.

In a study of serum levels of tumor necrosis factor (TNF alpha) and interleukin-1 beta (IL-1 beta) in patients developing sepsis in the ICU, high TNF alpha levels were found in patients with septic shock. Normal values are 75 +/- 15 pg/ml; in these patients, TNF alpha serum level ranged from 100 to 5000 pg/ml with a mean of 701 +/- 339 pg/ml and a median of 250 pg/ml. There was a correlation between TNF alpha level and sepsis severity score as well as with mortality. In contrast, IL-1 beta serum levels were only slightly increased and were not correlated with severity or mortality.

Hemodynamic changes during laparoscopic cholecystectomy.

Hemodynamics during laparoscopic cholecystectomy under general anesthesia (isoflurane in N2O/O2 (50%)) were investigated in 15 nonobese ASA Class I patients by using invasive hemodynamic monitoring including a flow-directed pulmonary artery catheter. During surgery, intraabdominal pressure was maintained automatically at 14 mm Hg by a CO2 insufflator, and minute ventilation was controlled and adjusted to avoid hypercapnia. Hemodynamics were measured before anesthesia, after the induction of anesthesia, after tilting into 10° head-up position, 5 min, 15 min, and 30 min after peritoneal insufflation, and 30 min after exsufflation. Induction of anesthesia decreased significantly mean arterial pressure and cardiac index (CI). Tilting the patient to the head-up position reduced cardiac pre-load and caused further reduction of CI. Peritoneal insufflation resulted in a significant increase (±35%) of mean arterial pressure, a significant reduction (±20%) of CI, and a significant increase of systemic (±65%) and pulmonary (±90%) vascular resistances. The combined effect of anesthesia, head-up tilt, and peritoneal insufflation produced a 50% decrease in CI. Administration of increasing concentrations of isoflurane, via its vasodilatory activity, may have partially blunted these hemodynamic changes. These results demonstrate that laparoscopy for cholecystectomy in head-up position results in significant hemodynamic changes in healthy patients, particularly at the induction of pneumoperitoneum.

Report of the American-European Consensus Conference on acute respiratory distress syndrome: Definitions, mechanisms, relevant outcomes, and clinical trial coordination

The acute respiratory distress syndrome (ARDS), a process of nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, carries a high morbidity rate, mortality rate (10% to 90%), and financial cost. The reported annual incidence in the United States is 150,000 cases, but this figure has been challenged and may be different in Europe. Part of the reason for these uncertainties is the heterogeneity of diseases underlying ARDS and the lack of uniform definitions for ARDS. Thus, those who wish to know the true incidence and outcome of this clinical syndrome are stymied. The European American Consensus Committee on ARDS was formed to focus on these issues and on the pathophysiologic mechanisms of the process. It was felt that international coordination between North America and Europe in clinical studies of ARDS was becoming increasingly important to address the recent plethora of potential therapeutic agents for the prevention and treatment of ARDS.

The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.

Restoration of thalamocortical connectivity after recovery from persistent vegetative state

By use of H2(15)O positron emission tomography we have shown that functional connectivity between intralaminar thalamic nuclei and prefrontal and anterior cingulate cortices was altered during vegetative state but not after recovery of consciousness.

Intravenous lidocaine infusion facilitates acute rehabilitation after laparoscopic colectomy

Background:Intravenous infusion of lidocaine decreases postoperative pain and speeds the return of bowel function. The authors therefore tested the hypothesis that perioperative lidocaine infusion facilitates acute rehabilitation protocol in patients undergoing laparoscopic colectomy. Methods:Forty patients scheduled to undergo laparoscopic colectomy were randomly allocated to receive intravenous lidocaine (bolus injection of 1.5 mg/kg lidocaine at induction of anesthesia, then a continuous infusion of 2 mg · kg−1 · h−1 intraoperatively and 1.33 mg · kg−1 · h−1 for 24 h postoperatively) or an equal volume of saline. All patients received similar intensive postoperative rehabilitation. Postoperative pain scores, opioid consumption, and fatigue scores were measured. Times to first flatus, defecation, and hospital discharge were recorded. Postoperative endocrine (cortisol and catecholamines) and metabolic (leukocytes, C-reactive protein, and glucose) responses were measured for 48 h. Data (presented as median [25–75% interquartile range], lidocaine vs. saline groups) were analyzed using Mann–Whitney tests. P < 0.05 was considered statistically significant. Results:Patient demographics were similar in the two groups. Times to first flatus (17 [11–24] vs. 28 [25–33] h; P < 0.001), defecation (28 [24–37] vs. 51 [41–70] h; P = 0.001), and hospital discharge (2 [2–3] vs. 3 [3–4] days; P = 0.001) were significantly shorter in patients who received lidocaine. Lidocaine significantly reduced opioid consumption (8 [5–18] vs. 22 [14–36] mg; P = 0.005) and postoperative pain and fatigue scores. In contrast, endocrine and metabolic responses were similar in the two groups. Conclusions:Intravenous lidocaine improves postoperative analgesia, fatigue, and bowel function after laparoscopic colectomy. These benefits are associated with a significant reduction in hospital stay.

Perception of pain in the minimally conscious state with PET activation: an observational study.

BACKGROUND Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance. METHODS We studied brain activation induced by bilateral electrical stimulation of the median nerve in five patients in MCS (aged 18-74 years) compared with 15 controls (19-64 years) and 15 patients (19-75 years) in a persistent vegetative state (PVS) with (15)O-radiolabelled water PET. By way of psychophysiological interaction analysis, we also investigated the functional connectivity of the primary somatosensory cortex (S1) in patients and controls. Patients in MCS were scanned 57 (SD 33) days after admission, and patients in PVS 36 (9) days after admission. Stimulation intensities were 8.6 (SD 6.7) mA in patients in MCS, 7.4 (5.9) mA in controls, and 14.2 (8.7) mA in patients in PVS. Significant results were thresholded at p values of less than 0.05 and corrected for multiple comparisons. FINDINGS In patients in MCS and in controls, noxious stimulation activated the thalamus, S1, and the secondary somatosensory or insular, frontoparietal, and anterior cingulate cortices (known as the pain matrix). No area was less activated in the patients in MCS than in the controls. All areas of the cortical pain matrix showed greater activation in patients in MCS than in those in PVS. Finally, in contrast with patients in PVS, those in MCS had preserved functional connectivity between S1 and a widespread cortical network that includes the frontoparietal associative cortices. INTERPRETATION Cerebral correlates of pain processing are found in a similar network in controls and patients in MCS but are much more widespread than in patients in PVS. These findings might be objective evidence of a potential pain perception capacity in patients in MCS, which supports the idea that these patients need analgesic treatment.

Pain after laparoscopic cholecystectomy : characteristics and effect of intraperitoneal bupivacaine

Although pain after laparoscopic cholecystectomy is less intense than after open cholecystectomy, some patients still experience considerable discomfort.Furthermore, the characteristics of post-laparoscopy pain differ considerably from those seen after laparotomy. Therefore, we investigated the time course of different pain components after laparoscopic cholecystectomy and the effects of intraperitoneal bupivacaine on these different components. Forty ASA physical status grade I-II patients were randomly assigned to receive either 80 mL of bupivacaine 0.125% with epinephrine 1/200,000 (n = 20) or the same volume of saline (n = 20) instilled under the right hemidiaphragm at the end of surgery. Intensity of total pain, visceral pain, parietal pain, and shoulder pain was assessed 1, 2, 4, 6, 8, 24, and 48 h after surgery. Analgesic consumption was also recorded. Patient data were similar in the two groups. In the saline group, visceral pain was significantly more intense than parietal pain at each time point; visceral and parietal pain were greater than shoulder pain during the first 8 h postoperatively. Intraperitoneal bupivacaine did not significantly affect any of the different components of postoperative pain. Analgesic consumption was similar in the two groups. This study demonstrates that visceral pain accounts for most of the pain experienced after laparoscopic cholecystectomy. Intraperitoneal bupivacaine is not effective for treating any type of pain after laparoscopic cholecystectomy. (Anesth Analg 1995;81:379-84)

Sepsis and serum cytokine concentrations.

OBJECTIVE To look for relationships between the classification of sepsis and plasma cytokine concentrations. DESIGN Prospective, consecutive entry study of patients meeting severe sepsis criteria and having bacteriologically documented infections. SETTING University hospital, surgical intensive care unit. PATIENTS Fifty consecutive patients developing severe sepsis or septic shock between December 1991 and December 1993. MEASUREMENTS AND MAIN RESULTS Concentrations of tumor necrosis factor, interleukin (IL)-6, IL-8, and leukemia inhibitory factor were measured by immunoradiometric assay in the plasma of patients as soon as they developed severe sepsis or septic shock. Septic shock patients were divided into three groups in a blinded fashion (i.e., without knowing the results of the concentrations of cytokines), according to the presence of sustained hyperlactacidemia and to the rapidity of the onset of sepsis. Peak concentrations of all cytokines were statistically different between severe sepsis and septic shock patients. This finding was almost exclusively due to the data from patients with rapid onset of septic shock, who demonstrated very high but transient cytokine concentrations. Septic shock patients may thus have different profiles in the time course of their cytokine concentrations. The transient, high peak concentrations of cytokines were also related to transient leukopenia. Among the cytokines measured, IL-8 appeared to be the one that correlated best with lactacidemia, the presence of disseminated intravascular coagulation, severe hypoxemia, the Acute Physiology and Chronic Health Evaluation II score, and mortality rate. CONCLUSIONS According to the profiles of the cytokines, septic shock patients do not represent a homogeneous population. These profiles should be described in order to distinguish between patients, and the profiles may be useful to identify those patients susceptible to new therapies.