Alexander Torossian

Independent risk factors for postoperative shivering.

Postoperative shivering (PAS) is uncomfortable for patients and potentially risky. In this observational trial we sought to identify independent risk factors for PAS after general anesthesia. Potential risk factors for PAS were recorded in 1340 consecutive patients. Signs of shivering, peripheral and core temperature, and thermal comfort were recorded in the postanesthetic care unit. The data were split into an evaluation data set (n = 1000) and a validation data set (n = 340). The first was used to identify independent risk factors for PAS and to formulate a risk score using backward-elimination logistic regression analysis. The proposed model was subsequently tested for its discrimination and calibration properties using receiver operating characteristic (ROC)-curve analysis and linear correlation between the predicted and the actual incidences of PAS in the validation group. The incidence of PAS was 11.6%. There were three major risk factors: young age, endoprosthetic surgery, and core hypothermia, with age being the most important. The risk score derived from this analysis had a reasonable discriminating power, with an area under the ROC-curve of 0.69 (95% confidence interval, 0.60–0.78; P < 0.0001). Furthermore the equation of the calibration curve (y = 0.69x + 6; R2 = 0.82; P < 0.05) indicated a good and statistically significant agreement between predicted and actual PAS incidence. Postoperative shivering can be predicted with acceptable accuracy using the four risk factors identified in the present study. The presented model may serve as a clinical tool to help clinicians to rationally administer prophylactic antishivering drugs.

Mild preseptic hypothermia is detrimental in rats

Objective:We evaluated the effects of mild hypothermia (32°C), established before experimental intra-abdominal sepsis, on outcome, cytokine pattern, and muscle tissue oxygenation. Design:Clinic modeling randomized laboratory trial. Setting:University laboratory. Subjects:Ninety-six male rats. Interventions:In a group-sequential design, using 42 rats per group, we compared mild hypothermia with normothermia before peritonitis. Peritoneal inoculation with human stool bacteria was performed to simulate clinical trial conditions. Additionally, 12 rats underwent preoperative mild hypothermia without infection. Measurements and Main Results:Primary end point was mortality at 120 hrs. Secondary end points were systemic cytokine concentrations, granulocyte counts, and muscle oxygen partial pressure. Survival rate was 40% (16 of 42) after preseptic hypothermia and 62% (26 of 42) after preseptic normothermia (p = .048). All hypothermic rats without infection survived. Interleukin-10 concentrations were 1843 ± 96 pg/mL after preseptic hypothermia, 945 ± 225 pg/mL with preseptic normothermia, and 520 ± 121 pg/mL after hypothermia without infection (p< .001). Macrophage inflammatory protein-2 was comparable in the treatment groups. Interleukin-6 concentrations were 106 ± 24 pg/mL after preseptic hypothermia and 276 ± 76 pg/mL with preseptic normothermia (p< .05). Postinfection granulocyte count was 1.7 × 109/L after hypothermia and 2.4 × 109/L after normothermia (p = .2). After infection, muscle oxygen partial pressure was 47 ± 10 mm Hg with preseptic hypothermia, 85 ± 12 mm Hg in preseptic normothermia, and 49 ± 9 mm Hg after hypothermia without infection (p = .7). Conclusions:In this rat model of intra-abdominal sepsis, mild preseptic hypothermia (32°C) reduced survival, impaired granulocyte recruitment, and changed cytokine balance, suggesting immunosuppression.

Preventing inadvertent perioperative hypothermia.

BACKGROUND 25-90% of all patients undergoing elective surgery suffer from inadvertent postoperative hypothermia, i.e., a core body temperature below 36°C. Compared to normothermic patients, these patients have more frequent wound infections (relative risk [RR] 3.25, 95% confidence interval [CI] 1.35-7.84), cardiac complications (RR 4.49, 95% CI 1.00-20.16), and blood transfusions (RR 1.33, 95% CI 1.06-1.66). Hypothermic patients feel uncomfortable, and shivering raises oxygen consumption by about 40%. METHODS This guideline is based on a systematic review of the literature up to and including October 2012 and a further one from November 2012 to August 2014. The recommendations were developed and agreed upon by representatives of five medical specialty societies in a structured consensus process. RESULTS The patients core temperature should be measured 1-2 hours before the start of anesthesia, and either continuously or every 15 minutes during surgery. Depending on the nature of the operation, the site of temperature measurement should be oral, naso-/oropharyngeal, esophageal, vesical, or tympanic (direct). The patient should be actively prewarmed 20-30 minutes before surgery to counteract the decline in temperature. Prewarmed patients must be actively warmed intraoperatively as well if the planned duration of anesthesia is longer than 60 minutes (without prewarming, 30 minutes). The ambient temperature in the operating room should be at least 21°C for adult patients and at least 24°C for children. Infusions and blood transfusions that are given at rates of >500 mL/h should be warmed first. Perioperatively, the largest possible area of the body surface should be thermally insulated. Emergence from general anesthesia should take place at normal body temperature. Postoperative hypothermia, if present, should be treated by the administration of convective or conductive heat until normothermia is achieved. Shivering can be treated with medications. CONCLUSION Inadvertent perioperative hypothermia can adversely affect the outcome of surgery and the patients postoperative course. It should be actively prevented.

Deleterious Effects of Mild Hypothermia in Septic Rats Are Ameliorated by Granulocyte Colony-stimulating Factor

Background The authors studied the effects of mild hypothermia on the outcome in a rat model of intraabdominal sepsis and tested whether granulocyte colony-stimulating factor (G-CSF) augments the host response and improves outcome during mild hypothermia. Methods A rat model of peritoneal contamination and infection with human stool bacteria was used to simulate clinical trials that included increasing complexity. In trial 1, postoperative hypothermia (32°C) was compared with normothermia (38°C), without supportive treatment (10 rats per group). In trial 2, with a more severe infection, rats were given antibiotic prophylaxis. Using 20 rats per group, the authors compared postoperative hypothermia (32°C), normothermia, and postoperative hypothermia (32°C) with 20 &mgr;g/kg G-CSF prophylaxis given 12 h before surgery and 12 h and 36 h after surgery. The primary endpoint was death at 120 h. Secondary endpoints were systemic cytokine concentrations, leukocyte counts, and the phagocytic activity of granulocytes and monocytes. Results In trial 1, 50% of the normothermia group and 10% of the postoperative hypothermia group survived. In trial 2, 50% of the normothermia group, 20% of the hypothermia group, and 60% of the hypothermia plus G-CSF group survived. Postoperative hypothermia plus G-CSF reduced plasma concentrations of interleukin-6 (hypothermia group, 511 ± 104 pg/ml; hypothermia plus G-CSF group, 247 ± 51 pg/ml) and macrophage inflammatory protein-2 (hypothermia group, 239 ± 43 pg/ml; hypothermia plus G-CSF group, 178 ± 21 pg/ml). Conclusions In this rat model of intraabdominal sepsis, postoperative hypothermia was deleterious. However, G-CSF treatment, initiated before contamination, reduced the mortality rate, increased the neutrophil count, and downgraded the systemic cytokine response.

EXIT (Ex utero Intrapartum Treatment) in lymphatic malformations of the head and neck: Discussion of three cases and proposal of an EXIT-TTP (Team Time Procedure) list

OBJECTIVES Ex utero Intrapartum Treatment (EXIT) is a technique to secure the fetal airway while oxygenation is maintained through utero-placental circulation. The aim of the study is to present three cases of fetal lymphatic malformation of the head and neck that required EXIT and to summarize EXIT details. METHODS The cases were studied before the delivery and EXIT was planned with a multidisciplinary team. The key factors of EXIT are considered and the type, stage and clinical score of the three lymphatic malformations are defined. RESULTS In the three cases of EXIT the time working on placental support to secure the airway was 9, 7, and 9 min, respectively (from the hysterotomy to clamping the umbilical cord). Procedures performed on the airway were laryngo-tracheo-bronchoscopy in the first case, laryngoscopy and intubation in the second one, laryngoscopy, drainage of the lymphatic macro-cyst, and intubation in the third case. A sketching to detail the EXIT steps are presented: EXIT-Team Time Procedure list (EXIT-TTP list). Lymphatic malformations were classified as mixed (micro/macro-cystic) in two cases, and macro-cystic in one. de Serres Stage was IV, V and II. Therapy varied in the three neonates (surgery alone, surgery+Picibanil+Nd-YAG, or Picibanil alone). CONCLUSIONS In case of prenatal suspicion of airway obstruction, EXIT should be planned with a multidisciplinary team. The EXIT-Team Time Procedure list (EXIT-TTP list), reviews the most critical phases of the procedure when different teams are working together. The type of lymphatic malformation, the anatomic location and the clinical score predict the outcome.

Basic life support with four different compression/ventilation ratios in a pig model: The need for ventilation ☆

BACKGROUND During cardiac arrest the paramount goal of basic life support (BLS) is the oxygenation of vital organs. Current recommendations are to combine chest compressions with ventilation in a fixed ratio of 30:2; however the optimum compression/ventilation ratio is still debatable. In our study we compared four different compression/ventilation ratios and documented their effects on the return of spontaneous circulation (ROSC), gas exchange, cerebral tissue oxygenation and haemodynamics in a pig model. METHODS Study was performed on 32 pigs under general anaesthesia with endotracheal intubation. Arterial and central venous lines were inserted. For continuous cerebral tissue oxygenation a Licox PtiO(2) probe was implanted. After 3 min of cardiac arrest (ventricular fibrillation) animals were randomized to a compression/ventilation-ratio 30:2, 100:5, 100:2 or compressions-only. Subsequently 10 min BLS, Advanced Life Support (ALS) was performed (100%O(2), 3 defibrillations, 1mg adrenaline i.v.). Data were analyzed with 2-factorial ANOVA. RESULTS ROSC was achieved in 4/8 (30:2), 5/8 (100:5), 2/8 (100:2) and 0/8 (compr-only) pigs. During BLS, PaCO(2) increased to 55 mm Hg (30:2), 68 mm Hg (100:5; p=0.0001), 66 mm Hg (100:2; p=0.002) and 72 mm Hg (compr-only; p<0.0001). PaO(2) decreased to 58 mmg (30:2), 40 mm Hg (100:5; p=0.15), 43 mm Hg (100:2; p=0.04) and 26 mm Hg (compr-only; p<0.0001). PtiO(2) baseline values were 12.7, 12.0, 11.1 and 10.0 mm Hg and decreased to 8.1 mm Hg (30:2), 4.1 mm Hg (100:5; p=0.08), 4.3 mm Hg (100:2; p=0.04), and 4.5 mm Hg (compr-only; p=0.69). CONCLUSIONS During BLS, a compression/ventilation-ratio of 100:5 seems to be equivalent to 30:2, while ratios of 100:2 or compressions-only detoriate peripheral arterial oxygenation and reduce the chance for ROSC.

Effects of the antimicrobial peptide LL-37 and hyperthermic preconditioning in septic rats.

Background:The authors tested the effects of LL-37 prophylaxis or therapy on the outcome after intraabdominal sepsis and examined whether hyperthermic preconditioning plus LL-37 therapy augments host immune response and improves survival. Methods:A rat model of peritoneal contamination and infection (PCI) with human stool was used to simulate clinical conditions. In trial 1, the authors compared (1) PCI, (2) LL-37 prophylaxis (0.5 mg/kg, 12 h before PCI), and (3) LL-37 therapy (0.5 mg/kg, 1 h after PCI). In trial 2, the authors compared (1) PCI, (2) LL-37 therapy, (3) hyperthermic preconditioning (41°C for 1 h, 24 h before PCI), and (4) LL-37 therapy and hyperthermic preconditioning. The primary endpoint was mortality at 120 h. In trial 2, secondary endpoints were systemic levels of tumor necrosis factor &agr;, interleukin 6, macrophage inflammatory protein 2, and heat shock protein 70; leukocyte counts; and neutrophil granulocyte phagocytosis. Results:In trial 1, 30% of the control group compared with 70% of the LL-37 therapy group survived, but 55% after LL-37 prophylaxis survived (P = 0.038). In trial 2, 38% of the controls, 67% of the LL-37 therapy, 59% of the hyperthermic preconditioned, and 90% of the hyperthermic preconditioned plus LL-37 therapy group survived (P = 0.01). LL-37 therapy plus hyperthermic preconditioning reduced proinflammatory cytokine concentrations after sepsis; specifically compared with controls, macrophage inflammatory protein-2 and interleukin-6 levels were 1.5 ± 1.5 versus 11 ± 6 pg/ml (P = 0.028) and 13 ± 8 versus 86 ± 31 pg/ml, (P = 0.015), respectively. Conclusions:In this model of intraabdominal sepsis, LL-37 therapy improved outcome. Hyperthermic preconditioning per se was not successful, but in combination with LL-37 therapy, the survival rate after sepsis was increased and the proinflammatory cytokine response was downgraded.

Dependence of Positive Effects of Granulocyte Colony-stimulating Factor on the Antibiotic Regimen: Evaluation in Rats with Polymicrobial Peritonitis

We tested the hypothesis that the ability of granulocyte colony-stimulating factor (G-CSF) to prevent death from fecal peritonitis is influenced by the composition of the antibiotic regimen with which it is administered. We used a rodent model of polymicrobial peritoneal contamination and infection and the concept of clinical modeling randomized trials (CMRTs), which includes the conditions of randomized, clinical trials and complex clinical interventions (e.g., anesthesia, volume substitution, antibiotics, surgery, postoperative analgesia). With the peritonitis model we obtained a mortality dose-response curve that was sensitive to antibiotic prophylaxis. G-CSF was most efficacious when it was administered both prophylactically and after the onset of peritonitis. Cefuroxime/metronidazole, ofloxacin/metronidazole, and amoxicillin/clavulanate improved survival in combination with G-CSF best, whereas cefotaxime or ceftriaxone with and without metronidazole did not. G-CSF administration was associated with improved polymorphonuclear neutrophil phagocytosis and enhanced bacterial clearance. Pro-inflammatory cytokine release (tumor necrosis factor-a, interleukin-6, macrophage inflammatory protein-2) was decreased in plasma and in the peritoneal fluid. Their expression was lowered in various organs on the protein and mRNA level. The results were used to design a clinical trial to test the ability of G-CSF to prevent serious infections in patients with colorectal cancer surgery. In this trial G-CSF application and antibiotic prophylaxis were performed with the most effective scheduling and combinations (cefuroxime/metronidazole and ofloxacin/metronidazole) as defined here.

Pre-treatment with ozonized oxygen (O3) aggravates inflammation in septic rats

AbstractObjective and design:Ozone is produced by neutrophils during bacterial killing. Its application was found to be beneficial in peritonitis patients. Therefore, we measured survival and cytokines after ozone pre-treatment in septic rats. Subjects and treatment:With approval, 40 male Wistar-rats were allocated to 1) ozone pre-treatment for five days before intra-abdominal sepsis, or 2) no pre-treatment. Methods:The primary endpoint was mortality at 120 h. Secondary endpoints were plasma cytokine levels. Results:In the control group mortality was 50% (10/20 rats). After ozone pre-treatment, survival was only 35% (7/20 rats, Log-Rank test: P = 0.10). Ozone increased TNF-α and MIP-2 after infection: 127±23 pg/ml and 94±19 pg/ml (control group: 398 pg/ml and 369 pg/ml; P < 0.002 and P < 0.01). IL-6 levels were similar in both groups. Conclusions:Ozone pre-treatment was pro-inflammatory in sepsis with a trend to reduced survival. Therefore, its effects in sepsis should be further evaluated in animal trials.

Mechanical vagus nerve stimulation--A new adjunct in sepsis prophylaxis and treatment?

Disease was long regarded as the result of the permanent battle between good and evil. Although terms have changed since ancient times and we nowadays talk about proand anti-inflammatory mechanisms, the paradigm of balance is still valid, particularly for infectious diseases. The balance is regulated by neuronal and biochemical mechanisms, establishing the neuroendocrine network. Key mediators in the immune-neuroendocrine network are earlyand late-response cytokines, such as tumor necrosis factor (TNF), interleukin (IL)-6, and high mobility group box 1 (HMGB1). These cytokines are crucial for the development of systemic inflammatory response syndrome, which is associated with high morbidity and mortality rates in various inflammatory diseases. Therefore, investigators have focused on influencing this fragile balance in a favorable way, for example, with antibodies against TNF or IL-10.