Therapy of hyperthermia in sepsis and septic shock. Necessary or injurious?

In critically ill patients fever is associated with an increased morbidity and mortality rate. However, it remains unclear whether fever is an associated symptom of the underlying severe disease or a stimulator of specific pathophysiological cascades considered responsible for a deleterious outcome. Hyperthermia per se induces systemic changes like increased energy and oxygen demands, tachycardia, or fluid loss which might be harmful especially in septic patients due to congestion of the cardiovascular system. In this constellation a reduction of fever by antipyretic strategies might be indicated to decrease oxygen and energy demands. On the other hand the increasing body temperature obviously plays an important role in the inflammatory hemostasis during infections. Fever optimises humoral and cellular responses to infection and has some direct effects on bacteria and other microorganisms. Therefore, in severe sepsis or septic shock, fever reduction might impair the immune competency of the patients. According to the currently available evidence a body temperature higher than 40 degrees C is definitely harmful and should be treated in any case. A temperature range between 36 degrees C and 39 degrees C should be achieved for patients with severe sepsis and septic shock. At present there are no data showing the superiority of any of the different antipyrectic strategies in septic patients. Hence, external cooling with cold blankets or other devices may induce shivering of the muscles with a substantial increase of oxygen demand and is hardly tolerated in conscious patients. However, antipyretic therapy in patients with severe sepsis or septic shock should be indicated while considering the individual pathophysiology of every patient.     

Which therapeutic prospects in the septic syndrome?

OBJECTIVE: To evaluate recent data provided on new treatments of patients with septic shock. DATA EXTRACTION: A Medline search was performed to identify pertinent literature on the pathophysiology of septic shock and treatment strategies from 1990 to 2003. Keywords were "septic shock", "sepsis", "inflammation" and "management". DATA SYNTHESIS: Advances were performed in our current understanding of pathophysiology of sepsis. The loss of homeostatic balance among the systemic inflammatory response and the disturbance of coagulation with generalized coagulopathy lead to organ failures and death. The administration of activated protein C (drotrecogin alfa) reducing this coagulopathy can decrease the mortality of septic shock patients. The modulation of inflammation did not make it possible to improve survival of septic shock patients until now. The efficacy of low doses of steroid has been recently shown in septic shock patients. In addition, new data highlighted the interest of an early goal therapy in patients with sepsis who are admitted to emergency. CONCLUSION: The improvement of survival in septic syndrome patients is a difficult challenge. The uses of different new therapeutic options like protein C reactive, steroids, or early goal therapy in association should make it possible to reduce the mortality in septic patients.     

Early preload adaptation in septic shock? A transesophageal echocardiographic study

BACKGROUND: An accepted concept in septic shock is that preload adaptation by acute left ventricular dilatation, when occurring spontaneously or with the aid of volume loading, permits maintenance of an adequate cardiac output, leading to final recovery. From a physiologic point of view, this concept appears debatable because a normal pericardium exerts a restraining action on a normal heart. METHODS: During a 26-month period, the authors investigated, by transesophageal echocardiography, 40 patients hospitalized in their unit for an episode of septic shock. Transesophageal echocardiography was performed in the first hours after admission, proceeded by correction of any hypovolemia, and stabilization of arterial pressure by vasoactive agent infusion if necessary. Left ventricular dimensions were obtained in long- and short-axis views, permitting calculation of left ventricular ejection fraction (long axis) and fractional area contraction (short axis). Stroke index was simultaneously measured by the Doppler technique. RESULTS: Stroke index was strongly correlated with both echocardiographic left ventricle ejection fraction (r = 0.75; P < 0.0001) and left ventricle fractional area contraction (r = 0.76; P < 0.0001), whereas it was independent of echocardiographic left ventricle diastolic dimensions. CONCLUSIONS: The transesophageal echocardiography study was unable to confirm the reality of the concept of early preload adaptation by left ventricular dilatation in septic shock. Conversely, because left ventricular volume always remained in a normal range after correcting hypovolemia, systolic function was the unique determinant of stroke index in septic shock.     

How well do serum sTREM-1 measurements prognosticate in septic shock?

The soluble triggering receptor expressed on myeloid cells (sTREM)-1 has emerged as a potentially useful biomarker for the diagnosis of sepsis. This study aimed to evaluate the prognostic utility of serum sTREM-1 in septic shock, in comparison with that of procalcitonin measurements. Thirty-one consecutive patients in a tertiary medical intensive care unit with septic shock were studied. sTREM-1 levels in blood were measured using a modified immunoblot array technique on days one to three of intensive care unit admission. Serum procalcitonin and interleukin (IL)-1beta, IL-6, IL-IO and tumour necrosis factor-alpha levels were also measured. No significant difference was observed in the sTREM-1 levels on the first three days between survivors and nonsurvivors. sTREM-1 levels moderately correlated with the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores on day three, but did not correlate with vasopressor requirements, cytokine levels and the presence of bacteraemia. In contrast, procalcitonin levels were significantly higher in nonsurvivors than in survivors on days two and three. A significant relationship also existed between procalcitonin levels and the other variables. In conclusion, this study found that the prognostic utility of serum sTREM-1 in septic shock is poor and that procalcitonin measurements perform better in this regard.     

How septic is urosepsis? Clinical course of infected hydronephrosis and therapeutic strategies

Despite rapid decompression of the upper urinary tract, some patients show signs of systemic inflammatory response syndrome (SIRS) or septic shock syndrome when infected hydronephrosis is diagnosed. Clinical and biological parameters were analyzed retrospectively in 189 patients diagnosed with hydronephrosis regarding disease severity as well as microbiological and antibiotic features. Fifty of the 189 patients had positive urine culture in the renal pelvis and were included in the study. Fifteen patients had to be placed in the intensive care unit and two patients developed severe septic signs. An initial body temperature above 38.5°C (P=0.0004) and an elevated BMI (P=0.002) were the only parameters that indicated a higher risk of developing SIRS or sepsis. Typical biological parameters were not helpful in differentiating patients who will develop urosepsis. Further research is necessary to provide conclusive evidence of the value of other early prognostic markers in patients with infected hydronephrosis.     

Relative adrenal insufficiency in etomidate-naïve patients with septic shock

A recent study reported that 77% of patients with septic shock had relative adrenal insufficiency. However, all patients were mechanically ventilated and received high-dose inotropes. In addition, at least 24% had prior exposure to etomidate, a drug known to suppress adrenal function. We studied the incidence of relative adrenal insufficiency in etomidate-na?ve patients with septic shock by analysing the adrenal response to high-dose short synacthen test in 113 consecutive patients from three university-affiliated intensive care units in Australia. Patients were allocated to three groups according to severity of illness and inclusion criteria of the trial of low dose hydrocortisone supplementation using information from patient records. Of the 113 patients, 98 had septic shock (Group A). The incidence of relative adrenal insufficiency in this subpopulation was 24.5%. Eighty-one per cent of patients with septic shock were mechanically ventilated (Group B). In this group, the incidence of relative adrenal insufficiency was 27.8%. Only 38 of the 98 patients with septic shock (39%) fulfilled inclusion criteria for the steroid supplementation trial (Group C). In this group, the incidence of relative adrenal insufficiency was only 34.2%. In all groups its presence was associated with a higher mortality. We conclude that the incidence of relative adrenal insufficiency in etomidate-naive septic shock patients was lower than observed in the steroid supplementation trial. Further, in those who fulfilled inclusion criteria for the trial, the incidence of relative adrenal insufficiency was half that reported by the trial. Our observations raise concerns about the generalizability of the findings of the above trial to etomidate-na?ve patients.     

Terminal complement complex in septic shock with capillary leakage: marker of complement activation?

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the value of terminal complement complex (C5b-9) plasma levels as a marker for complement activation in septic shock with concomitant capillary leak syndrome. METHODS: In a prospective animal study 10 fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.6 +/- 1.3 kg) were investigated over a period of 8 h. Sepsis was induced by faecal peritonitis (1 g kg(-1) body weight faeces, n = 5) and compared to controls (n = 5). The animals received 6% hydroxyethyl starch 200/0.5 to maintain a central venous pressure of 12 mmHg. To quantify capillary leak syndrome, albumin escape rate was measured using 99mTc-labelled human serum albumin. Plasma levels of terminal complement complex were measured in a double antibody immunoassay (neoepitope-specific MoAb aE 11 as catching antibody). Immunohistological studies of renal specimens were performed to detect terminal complement complex deposition. RESULTS: Albumen escape rate increased in septic animals (+ 52%) compared to controls (+ 3%, P < 0.05). Plasma levels of terminal complement complex decreased during the study period in both groups. In septic animals this finding was accompanied by a significant deposition of terminal complement complex in renal specimens (P < 0.05). CONCLUSION: We found an activation of the complement system proven by marked deposition of terminal complement complex in renal specimen, while its plasma levels decreased during the study period in septic and control animals. These results suggest that in septic shock with capillary leak syndrome plasma level of terminal complement complex may not be a reliable marker of complement activation.     

“Terlipressin in the treatment of septic shock: the earlier the better?”

Terlipressin, a long-acting vasopressinergic V1 agonist, is increasingly used to increase mean arterial blood pressure in the common setting of catecholamine-refractory septic shock. Traditionally, terlipressin has been used as drug of last resort and administered as intermittent high-dose bolus infusion (1-2 mg every 4 to 6 hours). Recent experimental and clinical evidence, however, suggests that terlipressin may also be used as a low-dose continuous infusion (1-2 microg kg(-1) h(-1)) in the early course of the disease. This approach may sufficiently increase systemic blood pressure and thereby prevent unwanted side effects, such as exaggerating increases in peripheral resistance or rebound hypotension. Small-scale clinical studies suggest that low-dose terlipressin, when given as a first-line vasopressor agent, is safe. Randomised, clinical multicenter trials are now needed to investigate whether or not early institution of low-dose continuous terlipressin infusion improves overall outcome of patients suffering from vasodilatory shock states.     

Late acute cardiac allograft rejection: new therapeutic options?

BACKGROUND: Late acute cellular rejection is associated with decreased survival and the development of CAV. Among new immunosuppressive drugs introduced into clinical practice, everolimus, has been shown to be safe in cardiac transplantation. We report our experience with everolimus in heart transplant recipients who developed late acute cellular cardiac rejection. METHODS: Patients with a history of previous rejection episodes who experienced cardiac rejection were switched to an everolimus, cyclosporine, and steroid immunosuppressive regimen. All patients had already received statins and antihypertensive medications. Everolimus, cyclosporine trough levels, and laboratory values were controlled monthly. Drug administration was adapted to an everolimus trough level between 3 and 8 ng/mL, mean maintenance dosage was 0.25 to 1.5 mg twice a day. Death, safety, side effects, biopsy-proven acute rejection episodes, laboratory values, and blood levels were evaluated retrospectively. RESULTS: Four cardiac allograft recipients (two male, two female), at a median of 1473.25 days post-orthotopic heart transplantation (oHTx) (range = 65 to 3045), received 1 to 1.5 mg everolimus per day. Over a follow-up period of at least 2 month (range = 2 to 10) the mortality was 0%. The drug was well tolerated; no acute cellular rejection greater than grade 1a (ISHLT grading) was observed after 2 months. In one patient increased cholesterol values and in two others, elevated triglyceride levels were seen, but were controlled with increased statin therapy. No obvious increased creatinine values were seen with everolimus. CONCLUSION: In conclusion, conversion to an everolimus-based immunosuppressive regimen after late cardiac rejection is safe and effective; no major side effects were observed.     

Correlation between extravascular lung water and oxygenation in ALI/ARDS patients in septic shock: possible role in the development of atelectasis?

This study aimed to evaluate the relationship between PaO2/FiO2 ratio and extravascular lung water in septic shock-induced acute respiratory distress syndrome in a prospective observational clinical trial. Twenty-three patients suffering from sepsis induced acute respiratory distress syndrome were recruited. All patients were ventilated in pressure control/support mode. Haemodynamic parameters were determined by arterial thermodilution (PiCCO) eight hourly for 72 hours. At the same time blood gas analyses were done and respiratory parameters were also recorded. Data are presented as mean +/-SD. For statistical analysis Pearson's correlation test, and analysis of variance (ANOVA) was used respectively. Significant negative correlation was found between extravascular lung water and PaO2/FiO2 (r = -0.355, P < 0.001), and significant positive correlation was shown between extravascular lung water and PEEP (r=0.557, P<0.001). A post-hoc analysis was performed when "low" PEEP: < 10 cmH2O and "high" PEEP: (10 cmH2O PEEP was applied, and neither the oxygenation, nor the driving pressure or the PaCO2 differed significantly, but the extravascular lung water showed significant difference when "high" or "low" PEEP was applied (13+/-5 vs 9+/-2 ml/kg respectively, P=0.001). This study found significant negative correlation between extravascular lung water and PaO2/FiO2. The mechanism by which extravascular lung water affects oxygenation is unknown but the significant positive correlation between PEEP and extravascular lung water shown in this trial suggests that the latter may have a role in the development of alveolar atelectasis.     

Anesthesia and sedation in the endoscopy suite? (influences and options)

Advances in technology and pharmacology have enabled gastrointestinal endoscopists to expand the diagnostic and therapeutic capabilities of the specialty. Research into the impact of the endoscopy environment on patient stress, acknowledgement of the various patient coping styles, development and deployment of procedural preparative programs and information streamlining have been shown to be of value in decreasing anxiety and reducing sedative requirements. Being aware of procedure-related stressors, and factors associated with complications, allows us to tailor our sedation or anesthesia plan to the individual patient.