Gau-Jun Tang

Tumor necrosis factor gene polymorphism and septic shock in surgical infection.

ObjectivesTo evaluate the relationship of the genotype distribution of the tumor necrosis factor (TNF)-&agr; polymorphism with regard to the plasma TNF-&agr; concentration and the development of septic shock as well as mortality of infected patients in a surgical intensive care unit (SICU). DesignA total of 112 postoperative critically ill infected patients were prospectively enrolled. SettingSICU of a tertiary university-affiliated medical center. PatientsPatients who were consecutively admitted to the SICU because of surgical infection with sepsis. InterventionBlood sampling. Measurements and Main ResultsBlood sample was obtained 24 hrs after intensive care unit (ICU) admission or within 2 hrs after the onset of septic shock to determine the plasma TNF-&agr; level and to analyze the genotype of the biallelic polymorphism of the TNF-&agr;. ResultsThe allele frequency of the TNF2 in our infected ICU patients was 12%. Forty-two (37.5%) patients admitted fulfilled the criteria of septic shock during their ICU stay. Patients carrying the TNF2 allele were not more likely to develop septic shock, nor did they have a higher mortality rate. In the patients with septic shock, those carrying the TNF2 allele had a significantly higher mortality rate than those with the homozygous TNF1 genotype (92% vs. 62%, p < .05). In those who developed septic shock, the TNF2 allele was significantly associated with higher TNF levels. ConclusionIn patients admitted to SICU with surgical infection, the frequency of TNF2 allele was higher than in the general population. SICU patients with TNF2 allele did not show a higher incidence of developing septic shock, nor was there a higher baseline TNF-&agr; level after infection. However, once septic shock had developed, the mortality rate was higher in those patients carrying the TNF2 allele.

Perioperative plasma concentrations of tumor necrosis factor-alpha and interleukin-6 in infected patients.

OBJECTIVE To characterize the sequential plasma concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and their relationship with the clinical outcome in patients with intra-abdominal infection who underwent surgical intervention. DESIGN A prospective, comparative study. SETTING Surgical intensive care unit of a university hospital. PATIENTS Fifteen patients with surgically proved intra-abdominal infection were included as the infected group. The comparative noninfected group consisted of ten patients who underwent major abdominal surgery without infection. INTERVENTIONS Blood samples were obtained from the indwelling arterial catheter before induction of general anesthesia, and 1, 1.5, 2, 3, 4, 6, and 24 hrs after skin incision. MEASUREMENTS AND MAIN RESULTS Plasma cytokine concentrations were measured using radioimmunoassay. The hemodynamic and physiologic parameters were recorded for comparison with cytokine concentrations. In the noninfected group, the TNF-alpha concentration was very low throughout the observation period, and the IL-6 concentration increased 4 hrs after skin incision. The infected group had significantly higher TNF-alpha and IL-6 concentrations than the noninfected group. The TNF-alpha concentration increased from 129.2 +/- 46.4 to 1196.0 +/- 445.8 pg/mL and the IL-6 concentration increased from 54.2 +/- 24.3 to 560.3 +/- 187.5 pg/mL 2 hrs after skin incision in the infected group. The postoperative APACHE II score correlated significantly with both peak IL-6 (r2=.39) and peak TNF-alpha (r2=.32) concentrations. CONCLUSIONS Both TNF-alpha and IL-6 concentrations increased significantly after surgical intervention in patients with intra-abdominal infection. The pulse increase in TNF-alpha concentration and the persistent increase in IL-6 concentration were related to the poor postoperative clinical condition in infected patients.

Effect of Transcutaneous Electrical Nerve Stimulation for Pain Relief on Patients Undergoing Hemorrhoidectomy: Prospective, Randomized, Controlled Trial

PURPOSE: Posthemorrhoidectomy pain control remains a challenging problem. Transcutaneous electrical nerve stimulation is known to be effective in the treatment of many diseases. Our aim was to investigate the effect of transcutaneous electrical nerve stimulation on pain relief in patients undergoing hemorrhoidectomy. METHODS: Sixty patients with symptomatic hemorrhoids were randomly allocated into two groups, the acupoint group (n=30) and the nonpoint control group (n=30). Transcutaneous electrical nerve stimulation was applied to those patients who received hemorrhoidectomy, and patient-controlled analgesia was achieved by injection of morphine through ambulatory infusion pumps. The dependent measures in this study were pain score from 0 (no pain) to 10 (agonizing pain), analgesic doses administrated through patient-controlled analgesia, and postoperative complications. RESULTS: The subjective pain scores evaluated 8, 12, 16, and 24 hours after hemorrhoidectomy in the control group and the acupoint group were 5.9±0.5 and 4.1±0.5, 5.7±0.5 and 3.5±0.4, 4.1±0.4 and 2.3±0.3, and 3.2±0.4 and 1.9±0.2, respectively (two-way analysis of variance;P<0.05). There was a significant difference between treatment groups in morphine use, with 11.6±2.2 mg in the control group and 6.2±1.3 mg in the acupoint group (P<0.05). The acupoint group tended to have less postoperative acute urinary retention (Fishers exact probability test;P=0.145) and less need for analgesics than the control group (P=0.112, Fishers exact test). CONCLUSION: Transcutaneous electrical nerve stimulation is effective for pain relief in patients receiving hemorrhoidectomy. Its efficacy and safety could assist outpatient pain management after hemorrhoidectomy.

Wood smoke extract promotes both apoptosis and proliferation in rat alveolar epithelial type II cells: the role of oxidative stress and heme oxygenase-1.

Objective:Inhalation of toxic smoke causes oxidant lung injury. Alveolar epithelial type II cells are important in the re-epithelialization of alveolar walls after lung injury. We investigated the responses of alveolar epithelial type II cells to insult by wood smoke extract, and we identified the role of reactive oxygen species and heme oxygenase-1 (an oxidative stress protein) in these responses. Design:A randomized, controlled study. Setting:A research laboratory. Subjects:Cultured rat L2 and primary alveolar epithelial type II cells. Interventions and Main Results:Exposure of L2 alveolar epithelial type II cells to smoke extract (60 &mgr;g/mL) caused increases in reactive oxygen species, mitogen-activated protein kinases phosphylation, heme oxygenase-1 expression, apoptosis, proliferation and cell population, all of which were largely reduced by N-acetylcysteine (an antioxidant). Additionally, the smoke extract-induced heme oxygenase-1 induction was significantly attenuated by mitogen-activated protein kinases inhibitors, by small interfering RNA targeting mitogen-activated protein kinases or by N-acetylcysteine. Furthermore, knockdown of heme oxygenase-1 by small interfering RNA prevented heme oxygenase-1 induction whereas increasing smoke extract-induced apoptosis and suppressing smoke extract-induced proliferation. Conversely, cobalt protoporphyrin IX (a heme oxygenase-1 inducer) amplified heme oxygenase-1 induction while suppressing smoke extract-induced apoptosis and augmenting smoke extract-induced proliferation. Consequently, the smoke extract-induced increase in cell population was changed into a decrease by heme oxygenase-1 small interfering RNA, but was further elevated by cobalt protoporphyrin IX. Smoke extract also caused increases in heme oxygenase-1 expression, apoptosis, proliferation and cell population in primary alveolar epithelial type II cells, and heme oxygenase-1 small interfering RNA similarly augmented smoke extract-induced apoptosis and suppressed smoke extract-induced proliferation in these primary cells. Conclusions:Smoke extract increases intracellular reactive oxygen species, which up-regulates heme oxygenase-1 via the mitogen-activated protein kinase pathways and also promotes both apoptosis and proliferation in rat alveolar epithelial type II cells. Additionally, smoke extract-induced heme oxygenase-1 induction counteracts smoke extract-induced apoptosis, but mediates smoke extract-induced proliferation, resulting in a net increase in cell population. Thus, in response to oxidant smoke insult, alveolar epithelial type II cells have evolved an adaptive mechanism involving heme oxygenase-1 that increases their cell population, presumably to help them perform their function of re-epithelialization following lung injury.

Peripheral neural modulation of endotoxin-induced hyperventilation.

OBJECTIVE To delineate the role of the peripheral neural reflexes involved in modulating hyperventilation during endotoxemia. DESIGN A prospective, randomized, controlled, multigroup study. SETTING Research animal laboratory. SUBJECTS Adult Sprague-Dawley rats (n=43; 354+/-24 g) of either gender. INTERVENTIONS Eight rats received a sham operation on their vagus, carotid sinus, and aortic nerves before the administration of a saline vehicle to serve as the time control. In the endotoxin group, 11 rats received a sham operation before endotoxin challenge. The remaining 24 rats received bilateral vagotomy (n=8), perivagal capsaicin treatment (n=8), or denervation of peripheral chemoreceptors (n=8) before endotoxin challenge. After the breathing pattern returned to a steady state, endotoxin (L-4130, serotype 0111, B4 lipopolysaccharide; 50 mg/kg) was injected into the vein. The rats respiration was then monitored continuously for 5 hrs or until the animal died. MEASUREMENTS AND MAIN RESULTS The respiratory rate and tidal volume did not change over the 5-hr observation period in the time control group. In the endotoxin group, the respiratory rate increased significantly from baseline (135.4%) 2 hrs after endotoxin challenge and increased persistently until the rats died. The tidal volume increased gradually to < or =132.8% of baseline 4 hrs after endotoxin challenge. Bilateral cervical vagotomy and perineural capsaicin treatment of the vagus nerves eliminated the tachypnea response to endotoxin injection. Denervation of the peripheral chemoreceptor accentuated the hyperventilation response to endotoxin, and resulted in the shortest survival time. CONCLUSIONS Both lung vagal C-fiber afferents and peripheral chemoreceptors are involved in modulating the hyperventilation response after endotoxin challenge in rat models. Stimulation of vagal C-fiber afferents increased the respiratory rate. Conversely, the role of peripheral chemoreceptors was to restrain the hyperventilatory response and these receptors may play a protective role during endotoxemia.

Alleviation of wood smoke-induced lung injury by tachykinin receptor antagonist and hydroxyl radical scavenger in guinea pigs.

We recently reported that wood smoke inhalation initially (within 5 min) causes airway injury and subsequently produces both airway and parenchymal injury after a delay (within 2 h). In this study, we investigated the mediator mechanisms of this delayed smoke-induced lung injury in 126 anesthetized and artificially ventilated guinea pigs who received challenges of either air or 40 tidal breaths of wood smoke. Two hours after inhalation, wood smoke produced various injurious responses, including increases in alveolar-capillary permeability, microvascular permeabilities, and histological injury scores, in airway and parenchymal tissues. Pre-treatment given before smoke challenge with CP-96,345 [a tachykinin NK1 receptor antagonist; (2S,3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)-methyl)-1-aza bicyclo(2.2.2.)-octan-3-amine], dimethylthiourea (a hydroxyl radical scavenger), or a combination of these two drugs largely alleviated both the airway and parenchymal responses, whereas pre-treatment with SR-48,968 [a tachykinin NK2 receptor antagonist; (S)-N-methyl-N(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophenyl)-butyl)benzamide] or a combination of CP-96,344 and SR-48,965 (inactive enantiomers) failed to do so. Post-treatment given at 5 min after smoke challenge with CP-96,345 or dimethylthiourea significantly alleviated the parenchymal responses, while having no effect on the airway responses. Pre-treatment with dimethylthiourea prevented the smoke-induced reduction in airway neutral endopeptidase activity (an enzyme for tachykinin degradation). We concluded that (1) tachykinins and hydroxyl radical play important roles in producing smoke-induced delayed lung injury in guinea pigs, and both may be involved in the spread of injury from the airways to the pulmonary parenchyma, and (2) the contribution of tachykinins is mediated via the activation of tachykinin NK1 receptors, and is associated with the hydroxyl radical-induced inactivation of airway neutral endopeptidase.

Readmission to the intensive care unit: A population-based approach

BACKGROUND/PURPOSE Readmission to the intensive care unit (ICU) results in increased consumption of medical resources and costs, and has been proposed as a marker for quality of care. ICU readmission rates have been estimated at 4-14% and different risk factors have been proposed by various studies. METHODS Every admission event to the ICU was recorded and readmission episodes were analyzed using a population-based database from the Taiwan National Health Insurance Research Database (NHIRD) for the period from January 1, 2006 to December 31, 2006. RESULTS The average follow-up time was 206.35 days. From the database of 192,201 patients admitted to the ICU, 25,263 patients were re-admitted, with a readmission rate of 13.13%. The leading etiologies for readmission were identified. Using multivariate analysis, age > 39 years old, female gender, ischemic heart disease, lung related disorders, pneumonia, cerebrovascular disease, sepsis, heart failure, chronic liver disease, diabetes mellitus, and chronic obstructive pulmonary disease were identified as significant risk factors for readmission to the ICU. CONCLUSION This study uses a novel approach to assess risk factors for readmission to the ICU. Higher risk patients should be assessed more carefully before discharge or transfer from the ICU to prevent readmission episodes.

Acute renal failure in severe pancreatitis: A population-based study

Abstract Introduction. Acute pancreatitis (AP) is a common illness with varied mortality and morbidity. Patients with AP complicated with acute renal failure (ARF) have higher mortality than patients with AP alone. Although ARF has been proposed as a leading mortality cause for AP patients admitted to the ICU, few studies have directly analyzed the relationship between AP and ARF. Methods. We performed a retrospective study using the population-based database from the Taiwan National Health Insurance Research Database (NHIRD). In the period from 1 January 2005 to 31 December 2005, every patient with AP admitted to the ICU was included and assessed for the presence of ARF and mortality risk. Results. In year 2005, there were a total of 221,101 admissions to the ICU. There were 1,734 patients with AP, of which 261 (15.05%) patients also had a diagnosis of ARF. Compared to sepsis and other critical illness, patients with AP had a higher risk of having a diagnosis of ARF, and patients with both diagnoses had a higher mortality rate in the same ICU hospitalization. Conclusion. AP is associated with a higher risk of ARF, and, when both conditions exist, a higher risk of mortality is present.

Successful Treatment of Severe Heatstroke With Therapeutic Hypothermia by a Noninvasive External Cooling System

Heatstroke is a life-threatening disease; however, no pharmacologic treatment has proven to be effective. In severe cases with multiple organ dysfunction, the mortality remains high and many patients inevitably develop permanent neurologic damage. We report a near-fatal case of exertional heatstroke with multiple organ dysfunction, including generalized convulsions, acute lung injury, and disseminated intravascular coagulation, successfully treated with induced therapeutic hypothermia (33°C [91.4°F]) by a noninvasive external cooling system. After treatment, the patient completely recovered, without any neurologic sequelae during 1 year of follow-up. To our knowledge, this is the first reported case of using therapeutic hypothermia in heatstroke.

Exacerbation of wood smoke-induced acute lung injury by mechanical ventilation using moderately high tidal volume in mice

We investigated the effects of mechanical ventilation with a moderately high tidal volume (VT) on acute lung injury (ALI) induced by wood smoke inhalation in anesthetized mice. Animals received challenges of air, 30 breaths of smoke (30SM) or 60 breaths of smoke (60SM) and were then ventilated with a VT of 10 ml/kg (10VT) or 16 ml/kg (16VT). After 4-h mechanical ventilation, the bronchoalveolar-capillary permeability, pulmonary infiltration of inflammatory cells, total lung injury score and pulmonary expressions of interleukin-1beta and macrophage inflammatory protein-2 mRNA and proteins in the 30SM+16VT and 60SM+16VT groups were greater than those in the 30SM+10VT and 60SM+10VT groups, respectively. Additionally, the wet/dry weight ratio of lung tissues and lung epithelial cell apoptosis in the 60SM+16VT group were greater than those in the 60SM+10VT group. These differences between the 16VT and 10VT groups were not seen in animals with air challenge. Thus, mechanical ventilation with a moderately high VT in mice exacerbates ALI induced by wood smoke inhalation.