Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

BACKGROUND Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. METHODS We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. RESULTS We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. CONCLUSIONS The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop strategies to integrate clinical patient-level data with administrative data to draw more accurate conclusions about the epidemiology of sepsis.

Normal values for pancreatic stone protein in different age groups.

BACKGROUND Pancreatic stone protein (PSP) has been identified as a promising sepsis marker in adults, children and neonates. However, data on population-based reference values are lacking. This study aimed to establish age-specific reference values for PSP. METHODS PSP was determined using a specific ELISA. PSP serum concentrations were determined in 372 healthy subjects including 217 neonates, 94 infants and children up to 16 years, and 61 adults. The adjacent categories method was used to determine which age categories had significantly different PSP concentrations. RESULTS PSP circulating levels were not gender-dependent and ranged from 1.0 to 99.4 ng/ml with a median of 9.2 ng/ml. PSP increased significantly between the age categories, from a median of 2.6 ng/ml in very preterm newborns, to 6.3 ng/ml in term newborns, to 16.1 ng/ml in older children (p < 0.001). PSP levels were higher on postnatal day three compared to levels measured immediately post delivery (p < 0.001). Paired umbilical artery and umbilical vein samples were strongly correlated (p < 0.001). Simultaneously obtained capillary heel-prick versus venous samples showed a good level of agreement for PSP (Rho 0.89, bias 19 %). CONCLUSIONS This study provides age-specific normal values that may be used to define cut-offs for future trials on PSP. We demonstrate an age-dependent increase of PSP from birth to childhood.

Cerebral Gaseous Microemboli are Detectable During Continuous Venovenous Hemodialysis in Critically Ill Patients: An Observational Pilot Study

BACKGROUND Continuous venovenous hemodialysis (CVVHD) may generate microemboli that cross the pulmonary circulation and reach the brain. The aim of the present study was to quantify (load per time interval) and qualify (gaseous vs. solid) cerebral microemboli (CME), detected as high-intensity transient signals, using transcranial Doppler ultrasound. MATERIALS AND METHODS Twenty intensive care unit (ICU group) patients requiring CVVHD were examined. CME were recorded in both middle cerebral arteries for 30 minutes during CVVHD and a CVVHD-free interval. Twenty additional patients, hospitalized for orthopedic surgery, served as a non-ICU control group. Statistical analyses were performed using the Mann-Whitney U test or the Wilcoxon matched-pairs signed-rank test, followed by Bonferroni corrections for multiple comparisons. RESULTS In the non-ICU group, 48 (14.5-169.5) (median [range]) gaseous CME were detected. In the ICU group, the 67.5 (14.5-588.5) gaseous CME detected during the CVVHD-free interval increased 5-fold to 344.5 (59-1019) during CVVHD (P<0.001). The number of solid CME was low in all groups (non-ICU group: 2 [0-5.5]; ICU group CVVHD-free interval: 1.5 [0-14.25]; ICU group during CVVHD: 7 [3-27.75]). CONCLUSIONS This observational pilot study shows that CVVHD was associated with a higher gaseous but not solid CME burden in critically ill patients. Although the differentiation between gaseous and solid CME remains challenging, our finding may support the hypothesis of microbubble generation in the CVVHD circuit and its transpulmonary translocation toward the intracranial circulation. Importantly, the impact of gaseous and solid CME generated during CVVHD on brain integrity of critically ill patients currently remains unknown and is highly debated.

Which Anesthesia Regimen Is Best to Reduce Morbidity and Mortality in Lung Surgery? A Multicenter Randomized Controlled Trial.

BACKGROUND One-lung ventilation during thoracic surgery is associated with hypoxia-reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia-induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications. METHODS Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age. RESULTS Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). CONCLUSIONS This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident.

Impact of a Potassium-enriched, Chloride-depleted 5% Glucose Solution on Gastrointestinal Function after Major Abdominopelvic Surgery: Results of a Randomized Controlled Trial.

BACKGROUND Gastrointestinal (GI) complications often delay recovery after radical cystectomy with urinary diversion. The authors investigated if perioperative administration of a potassium-enriched, chloride-depleted 5% glucose solution (G5K) accelerates recovery of GI function. METHODS This randomized, parallel-group, single-center double-blind trial included 44 consecutive patients undergoing radical cystectomy and pelvic lymph node dissection with urinary diversion. Patients were randomized to receive either a G5K (G5K group) solution or a Ringer's maleate solution (control group). Fluid management aimed for a zero fluid balance. Primary endpoint was time to first defecation. Secondary endpoints were time to normal GI function, need for electrolyte substitution, and renal dysfunction. RESULTS Time to first defecation was not significantly different between groups (G5K group, 93 h [19 to 168 h] and control group, 120 h [43 to 241 h]); estimator of the group difference, -16 (95% CI, -38 to 6); P = 0.173. Return of normal GI function occurred faster in the G5K group than in the control group (median, 138 h [range, 54 to 262 h] vs. 169 h [108 to 318 h]); estimator of the group difference, -38 (95% CI, -74 to -12); P = 0.004. Potassium and magnesium were less frequently substituted in the G5K group (13.6 vs. 54.5% [P = 0.010] and 18.2 vs. 77.3% [P < 0.001]), respectively. The incidence of renal dysfunction (Risk, Injury, Failure, Loss and End-stage kidney disease stage "risk") at discharge was 9.1% in the G5K group and 4.5% in the control group; P = 1.000. CONCLUSIONS Perioperative administration of a G5K did not enhance first defecation, but may accelerate recovery of normal GI function, and reduces potassium and magnesium substitution after radical cystectomy and urinary diversion.

Causes of death of anesthesiologists from the chloroform era /

"Grant no. R805473-01."

Current researches in anesthesia & analgesia.

Mode of access: Internet.

Comparison of Analgesic Outcomes Following Sciatic Nerve Blockade Performed by Resident Trainees and Nurse Anesthetists

Background and objectives: Peripheral nerve blockade requires regional anesthesia skills that are taught in several formats and assessing technical proficiency has shifted from fulfillment of quotas to comprehensive procedural evaluation. Complete analgesia is the clinical endpoint validating successful nerve blockade but patient, technical and procedural factors influence this result. The purpose of this study was to determine if physician trainee or nurse anesthetist administered sciatic nerve blockade influence postoperative pain scores and opioid analgesic requirements and if patient factors, technique and repetition influence this outcome. Method: Sciatic nerve blockade by nerve stimulation and ultrasound based techniques were performed by senior anesthesiology resident trainees and nurse anesthetists under the supervision of regional anesthesia faculty. Preoperative patient characteristics including obesity, trauma, chronic pain, opioid use and preoperative pain scores were recorded and compared to the post-procedure pain scores and opioid analgesic requirements upon discharge from the post-anesthesia care unit and 24 hours following sciatic nerve blockade. Results: 93 patients received sciatic nerve blockade from 22 nurse anesthetists and 21 residents during 36 months. A significant relation between training background and improved pain scores was not demonstrated but transition from nerve stimulation to ultrasound guided techniques lowered immediate opioid usage in all groups. Patients with pre-existing chronic opioid use had higher postoperative pain scores and opioid dosages following nerve block. Conclusion: Patient analgesia should be an integral measure of proficiency in regional anesthesia techniques and evaluating this procedure outcome for all practitioners throughout their training and beyond graduation will longitudinally assess technical expertise.

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery

Hypersensitivity to a variety of sensory Stimuli is a feature of persistent whiplash associated disorders (WAD). However, little is known about sensory disturbances from the time Of injury until transition to either recovery or symptom persistence. Quantitative sensory testing (pressure and thermal pain thresholds, the brachial plexus provocation test), the sympathetic vasoconstrictor reflex and psychological distress (GHQ-28) were prospectively measured in 76 whiplash Subjects within 1 month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered (30). Sensory and sympathetic nervous system tests were also measured in 20 control subjects. All whiplash groups demonstrated local mechanical hyperalgesia in the cervica spine at 1 month post-injury. This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms. Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests. These changes Occurred within 1 month of injury and remained Unchanged throughout the Study period. Whilst no significant group differences were evident for the sympathetic vasoconstrictor response, the moderate/severe group showed a tendency for diminished sympathetic reactivity. GHQ-28 scores of the moderate/severe group were higher than those of the other two groups. The differences in GHQ-28 did not impact on any of the sensory measures. These findings suggest that those with persistent moderate/severe symptoms at 6 months display, soon after injury, generalised hypersensitivity suggestive of changes in central pain processing mechanisms. This phenomenon did not Occur in those who recover or those with persistent mild symptoms. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

Cefepime versus cefpirome: The importance of creatinine clearance

Standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients without renal dysfunction. We compared the pharmacokinetics of two fourth-generation cephalosporins, cefepime and cefpirome, and examined the relationship of drug clearance (CL) to creatinine clearance (CLCR). Two separate but similar pharmacokinetic studies (which used 2 g twice daily for each antibiotic) were conducted. Blood was sampled after an initial and a subsequent antibiotic dose. Drug plasma concentrations were measured, and pharmacokinetic analyses were conducted and compared. The pharmacokinetics of cefepime and cefpirome are similar in IC patients. Any differences in drug CL can largely be attributed to differences in CLCR. Despite normal plasma creatinine concentrations, 54% of patients' antibiotic concentrations were less than the minimum inhibitory concentration (MIC) (4 mg/L) for >20% of the dosing interval. Thirty-four percent of patients had CLCR >144 mL/min (20% higher than the expected maximum of 120 mL/min). Only CLCR was an independent predictor of antibiotic CL. Time above MIC was predicted only by CLCR. Some IC patients have a very large CLCR which results in very low levels of studied antibiotics. Either shortening the dosage interval or using continuous infusions would prevent low levels and keep troughs above the MIC for longer periods. In view of the lack of bedside measurement of cephalosporin levels, we suggest that more frequent use be made of CLCR to allow prediction of small concentrations clinically.

The development of psychological changes following whiplash injury

Psychological distress is a feature of chronic whiplash-associated disorders, but little is known of psychological changes from soon after injury to either recovery or symptom persistence. This study prospectively measured psychological distress (General Health Questionnaire 28 GHQ-28). fear of movement/re-injury (TAMPA Scale of Kinesphobia, TSK), acute post-traumatic stress (Impact of Events Scale, IES) and general health and well being (Short Form 36, SF-36) in 76 whiplash subjects within I month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered (< 8), mild pain and disability (10-28) or moderate/severe pain and disability (> 30). All whiplash groups demonstrated psychological distress (GHQ-28, SF-36) to some extent at 1 month post-injury. Scores of the recovered group and those with persistent mild symptoms returned to levels regarded as normal by 2 months post-injury, parallelling a decrease in reported pain and disability. Scores on both these tests remained above threshold levels in those with ongoing moderate/severe symptoms. The moderate/severe and mild groups showed elevated TSK scores at 1 month post-injury. TSK scores decreased by 2 months in the group with residual mild symptoms and by 6 months in those with persistent moderate/severe symptoms. Elevated IES scores, indicative of a moderate post-traumatic stress reaction, were unique to the group with moderate/severe symptoms. The results of this study demonstrated that all those experiencing whiplash injury display initial psychological distress that decreased in those whose symptoms subside. Whiplash participants who reported persistent moderate/severe symptoms at 6 months continue to be psychologically distressed and are also characterised by a moderate post-traumatic stress reaction. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Morphine-3-glucuronide's neuro-excitatory effects are mediated via indirect activation of N-methyl-D-aspartic acid receptors: Mechanistic studies in embryonic cultured hippocampal neurones

Indirect evidence indicates that morphine-3-glucuronide (M3G) may contribute significantly to the neuro-excitatory side effects (myoclonus and allodynia) of large-dose systemic morphine. To gain insight into the mechanism underlying M3G' s excitatory behaviors, We used fluo-3 fluorescence digital imaging techniques to assess the acute effects of M3G (5-500 muM) on the cytosolic calcium concentration ([Ca2+](CYT)) in cultured embryonic hippocampal neurones. Acute (3 min) exposure of neurones to M3G evoked [Ca2+](CYT) transients that were typically either (a) transient oscillatory responses characterized by a rapid increase in [Ca2+](CYT) oscillation amplitude that was sustained for at least similar to30 s or (b) a sustained increase in [Ca2+](CYT) that slowly recovered to baseline. Naloxone-pretreatment decreased the proportion of M3G-responsive neurones by 10%-25%, implicating a predominantly non-opioidergic mechanism. Although the naloxone-insensitive M3G-induced increases in [Ca2+](CYT) were completely blocked by N-methyl-D-aspartic acid (NMDA) antagonists and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (alphaamino-3-hydroxy-5-methyl-4-isoxazolepropiordc acid/ kainate antagonist), CNQX did not block the large increase in [Ca2+](CYT) evoked by NMDA (as expected), confirming that N13G indirectly activates the NMDA receptor. Additionally, tetrodotoxin (Na+ channel blocker), baclofen (gamma-aminobutyric acid, agonist), MVIIC (P/Q-type calcium channel blocker), and nifedipine (L-type calcium channel blocker) all abolished M3G-induced increases in [Ca2+](CYT), suggesting that M3G may produce its neuro-excitatory effects by modulating neurotransmitter release. However, additional characterization is required.

Neck flexor muscle fatigue is side specific in patients with unilateral neck pain

Despite the evidence of greater fatigability of the cervical flexor muscles in neck pain patients, the effect of unilaterality of neck pain on muscle fatigue has not been investigated. This study compared myoelectric manifestations of sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue between the painful and non-painful sides in patients with chronic unilateral neck pain. Myoelectric signals were recorded from the sternal head of SCM and the AS muscles bilaterally during sub-maximal isometric cervical flexion contractions at 25% and 50% of the maximum voluntary contraction (MVC). The time course of the mean power frequency, average rectified value and conduction velocity of the electromyographic signals were calculated to quantify myoelectric manifestations of muscle fatigue. Results revealed greater estimates of the initial value and slope of the mean frequency for both the SCM and AS muscles on the side of the patient's neck pain at 25% and 50% of MVC. These results indicate greater myoelectric manifestations of muscle fatigue of the superficial cervical flexor muscles ipsilateral to the side of pain. This suggests a specificity of the effect of pain on muscle function and hence the need for specificity of therapeutic exercise in the management of neck pain patients. (C) 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Reduction of β-Endorphin-Containing Immune Cells in Inflamed Paw Tissue Corresponds with a Reduction in Immune-Derived Antinociception: Reversible by Donor Activated Lymphocytes

The functional integrity of the immune system is essential for peripheral antinociception. Previous studies have demonstrated that immune cells elicit potent antinociception in inflamed tissues and that corticotropin-releasing factor-induced antinociception is significantly inhibited in animals that have undergone cyclosporin A (CsA)-induced immunosuppression. In this study, we examined the effect of a single bolus of CsA on inflammatory nociception. CsA-treated rats had substantially increased nociception compared with nonimmunosuppressed rats, consistent with a reduction in circulating and infiltrating lymphocytes. Furthermore, CsA-treated rats had inhibition of corticotropin-releasing factor-induced immune-derived antinociception, which was dose-dependently reversed by IV injection of concanavalin A-activated donor lymphocytes (1.0-7.0 X 10(6) cells/0.1 mL). In conclusion, our findings provided further evidence that opioid-containing immune cells are essential for peripheral analgesia. It is evident from these findings that control of inflammatory pain relies heavily on a functioning immune system.