Minna Tallgren

Long-term survival, quality of life, and quality-adjusted life-years among critically ill elderly patients*

Objectives:To assess mortality, quality of life (QOL), and quality-adjusted life-years (QALYs) for critically ill elderly patients. Design:Cross-sectional survey. Setting:A ten-bed medical-surgical intensive care unit (ICU) in a tertiary care university hospital. Patients:The study group included 882 elderly patients (≥65 yrs of age) and 1,827 controls (<65 yrs of age) treated during the period of 1995 to 2000. Intervention:None. Measurements and Main Results:Mortality was assessed during the ICU and hospital stays, and 12, 24, and 36 months after ICU discharge. The cumulative 3-yr mortality rate among the elderly (57%) was higher (p < .05) than that among the controls (40%). The majority (66%) of the elderly nonsurvivors died within 1 month after intensive care discharge. All elderly patients with day-1 Sequential Organ Failure (SOFA) scores >15 died during the ICU stay. QOL was assessed with EQ-5D and RAND-36 measures from 10 months to 7 yrs after discharge. The majority (88%) of the elderly survivors assessed their present health state as good or satisfactory; 66% found it to be similar or better than 12 months earlier, and 48% similar or better than their preadmission state. QOL measures by RAND-36 revealed that aging decreased their competencies most in physical functioning, physical role limitations, and vitality, but the elderly had better values in mental health than the controls. However, QALYs of the elderly respondents were 21% to 35% lower than the mean QALY minus 2 sd units of the age- and gender-adjusted general population. Conclusions:High age alone is not a valid reason to refuse intensive care, but the benefits perceived by intensive care seem to decrease with aging, if reflected as QALYs. However, 97% of the elderly survivors lived at home and 88% of them considered their QOL satisfactory or good after hospital discharge. Therefore, more reliable information on the outcome for the elderly is clearly needed.

N-acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double-blind, placebo-controlled trial.

In this prospective, randomized, placebo-controlled, double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery. Seventy patients without previously documented renal dysfunction were randomly allocated to receive either N-acetylcysteine (150 mg/kg mixed in 250 mL of 5% dextrose infused in 20 min, followed by an infusion of 150 mg/kg in 250 mL of 5% dextrose over 24 h) or placebo. The infusion was started after the induction of anesthesia. The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-β-d-glucosaminidase (NAG)/creatinine ratio (indicator of renal tubular injury) and urinary albumin/creatinine ratio (indicator of glomerular injury). Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations. The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups. The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group. However, the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups. Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups. In conclusion, N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function, and some degree of tubular injury seems to occur before aortic crossclamp.

The Effective Analgesic Dose of Dexamethasone After Laparoscopic Hysterectomy

BACKGROUND: Apart from being antiemetic, glucocorticoids have an analgesic property. The optimal dose of dexamethasone in the management of pain after surgery has not been established. In this placebo-controlled, dose-finding study, we evaluated the analgesic effect of three doses of dexamethasone after laparoscopic hysterectomy. METHODS: We randomized 129 women scheduled for laparoscopic hysterectomy to receive placebo, dexamethasone 5 mg (D5), 10 mg (D10), or 15 mg (D15) IV before the induction of anesthesia. The patients were anesthetized with propofol and remifentanil in a standardized manner. Until the first postoperative morning, postoperative pain was managed with IV oxycodone using patient-controlled analgesia. The visual analog scale scores for pain and side effects, and the amounts of the analgesics were recorded for 3 days after surgery. RESULTS: The total dose of oxycodone (0–24 h after surgery) was smaller in the D15 (0.34 mg/kg [0.11–0.87]) group than in the placebo group (0.55 mg/kg [0.19–1.13]) (P = 0.003). The doses of oxycodone during Hours 0–2 after surgery were smaller in the D10 (0.17 mg/kg [0.03–0.36]) and D15 (0.17 mg/kg [0.03–0.35]) groups than in the placebo (0.26 mg/kg [0.10–0.48]) (P = 0.001, D10 versus placebo; P < 0.001, D15 versus placebo) group. During Hours 2–24 after surgery, however, the doses of oxycodone were equal in the placebo, D5, D10, and D15 groups (0.31 mg/kg [0.03–0.78], 0.22 mg/kg [0.03–0.92], 0.24 mg/kg [0.05–0.87], and 0.20 mg/kg [0–0.65], respectively). The visual analog scale scores for pain at rest, in motion, or at cough did not differ in the study groups. The incidence of dizziness was lower in the D15 group than in the placebo group (P = 0.001), the D5 group (P = 0.006), and the D10 group (P = 0.030) during the first 24 h after surgery. During the later course of recovery, the incidence of dizziness did not differ among the four study groups. CONCLUSIONS: IV dexamethasone 15 mg before induction of anesthesia decreases the oxycodone consumption during the first 24 h after laparoscopic hysterectomy. During first 2 h after surgery, dexamethasone 10 mg reduces the oxycodone consumption as effectively as the 15 mg dose.

Modified score for disseminated intravascular coagulation in the critically ill.

ObjectiveTo assess the value of the diagnosis of overt disseminated intravascular coagulation (DIC) according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and that of the parameters included in the ISTH score for overt DIC in predicting day 28 mortality in intensive care patients. Also, to assess the value of the components of the score in the diagnosis of overt DIC.Design and settingRetrospective clinical study in a university hospital intensive care unit.Patients and participants494 consecutive patients admitted in the ICU between January 2002 and October 2003.Measurements and resultsClinical and laboratory data, including hemostatic parameters, were collected from computerized databases and patient files. Altogether 19% (95/494) of the patients fulfilled the criteria for overt DIC. Their day 28 mortality rate was higher than that of patients without overt DIC (40% vs. 16%). The lowest platelet count (area under curve, AUC, 0.910), highest plasma D-dimer (AUC 0.846), lowest antithrombin (AUC 0.823), and Owren-type prothrombin time activity (AUC 0.797) discriminated well the patients with and without overt DIC, whereas plasma fibrinogen (AUC 0.690) had poor discriminative power. No patient with the diagnosis of overt DIC had decreased plasma fibrinogen. Day-1 SOFA and APACHE II score, the first CRP measurement, and the lowest antithrombin were independent predictors of day 28 mortality.ConclusionsThe diagnosis of overt DIC was not an independent predictor of day 28 mortality. In ICU patients plasma antithrombin seems a promising candidate in the panel of indicators for overt DIC whereas the value of plasma fibrinogen is in doubt.

Pain in 1,000 women treated for breast cancer: a prospective study of pain sensitivity and postoperative pain.

Background:This article describes the methods and results of the early part (experimental pain tests and postoperative analgesia) of a study that assesses genetic and other factors related to acute pain and persistent pain after treatment of breast cancer in a prospective cohort of 1,000 women. Methods:One thousand consenting patients were recruited to the study. Before surgery (breast resection or mastectomy with axillary surgery), the patients filled in questionnaires about health, life style, depression (Beck Depression Inventory), and anxiety (State-Trait Anxiety Inventory). They were also exposed to experimental tests measuring heat (43° and 48°C, 5 s) and cold (2-4°C) pain intensity and tolerance. Anesthesia was standardized with propofol and remifentanil, and postoperative analgesia was optimized with i.v. oxycodone. Results:The patients showed significant interindividual variation in heat and cold pain sensitivity and cold pain tolerance. There was a strong correlation between the experimental pain measures across the tests. Presence of chronic pain, the number of previous operations, and particularly state anxiety were related to increased pain sensitivity. Previous smoking correlated with decreased heat pain sensitivity. These factors explained 4–5% of the total variance in pain sensitivity in these tests. Oxycodone consumption during 20 h was significantly higher in patients who had axillary clearance. Oxycodone consumption had only a weak correlation with the experimental pain measures. Conclusions:Contact heat and cold pressure tests identify variability in pain sensitivity which is modified by factors such as anxiety, chronic pain, previous surgery, and smoking. High levels of anxiety are connected to increased pain sensitivity in experimental and acute postoperative pain.In a study of 1,000 women undergoing breast surgery for cancer, a small portion of the variance in preoperative response to noxious heat and cold testing could be explained by anxiety, the presence of chronic pain, and the number of previous operations. There was a weak correlation between response to experimental pain testing and acute postoperative pain, with largely similar predictive factors across both.

APCAP - activated protein C in acute pancreatitis: a double-blind randomized human pilot trial

IntroductionPrevious human studies have shown low activity of protein C (APC) in severe acute pancreatitis (SAP). This, together with the findings in animal models, suggests that activated protein C (APC) may protect against pancreatic injury and ameliorate the disease. We, therefore, evaluated its effect on multiple organ dysfunction (MOD) measured by the SOFA (Sequential Organ Failure Assessment) and on organ-failure-free days, and the safety of APC in SAP.MethodsA prospective double blind randomized pilot study was use. The study occurred in one university hospital tertiary intensive care unit (ICU) with eight beds. The patients were chosen according to the following inclusion criteria: 1) Those admitted to the hospital < 96 h from the onset of pain, 2) Those who had a three-fold increase in serum amylase over normal upper range or/and in whom computed tomography (CT) verification of SAP was noted, 3) Those who had one or more organ dysfunction (OD), and 4) Those in whom less than 48 hours had passed since their first OD. Of a total of 215 adult patients with SAP screened between June 2003 and August 2007, 158 fulfilled the study inclusion criteria. After exclusions 32 patients were randomized to the study. The intervention consisted of APC (N = 16) administered intravenously for 96 hours with a dose of 24 μg/kg/hour or placebo (N = 16) with a similar infusion rate. The sample size for the study was calculated according to the primary end-point: the change in SOFA during study drug infusion (Days 0 and 5). Comparisons between the study groups were performed using patient-related changes and calculation of difference in means (DIM, 95% CIs) and regarding categorical variables with Fishers exact test. For all comparisons P < 0.05 was considered significant.ResultsNo serious bleeding was detected clinically or by CT scans in either group. No significant difference in SOFA score change between the APC and placebo groups was found (difference in means (DIM) +2.3, 95% CI -0.7 to +5.3). Treatment with APC was associated with an increase in serum levels of both total and conjugated bilirubin. No differences in ventilator-free days, in renal replacement therapy-free days, in vasopressor-free days, or in days alive outside the hospital were detected.ConclusionsNo serious bleeding or differences in the evolution of MOD were detected between APC and the placebo. Instead we found an increase in serum bilirubin in the APC group compared to the placebo group in patients with SAP.Trial registrationClinicalTrials.gov NCT01017107.

Hepatic and splanchnic oxygenation during liver transplantation.

OBJECTIVE To evaluate hepatic and splanchnic oxygenation during liver transplantation. DESIGN Prospective study. SETTING University hospital. PATIENTS Ten adult patients undergoing liver transplantation. INTERVENTIONS Standardized surgery and anesthesia without venovenous bypass. MEASUREMENTS AND MAIN RESULTS Hepatic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in hepatic venous blood. Splanchnic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in portal venous blood and by gastric tonometry. Before reperfusion, the grafts were flushed with 1000 mL of acetated Ringers solution and 400 mL of portal venous blood. The effluent blood from the graft was wasted and showed a mean pH of 6.86 and a lactate concentration of 9.4 mmol/L. Five minutes after portal reperfusion, most of the grafts produced lactate. Portal-hepatic venous P(CO2) difference ranged from 3 to 16 torr (0.4-2.1 kPa). By the time of restoration of the infrahepatic caval flow mean 24 mins later, eight of the grafts had stopped producing lactate. Mean hepatic venous oxygen tension was 47 torr (6.3 kPa), stabilizing to 41 torr (5.5 kPa) at the end of surgery. Acidosis resolved without pharmacologic interventions. Mean gastric mucosal pH was 7.29 during the anhepatic phase and 7.40 at the end of surgery. One of the patients developed hepatic arterial thrombosis intraoperatively. Her data were analyzed separately. Later, the other patients recovered with good liver function, whereas the patient with hepatic arterial thrombosis was successfully retransplanted. CONCLUSIONS The liver grafts received well-oxygenated portal venous blood during reperfusion, despite the low values of gastric mucosal pH immediately before reperfusion. Hepatic oxygenation became adequate soon after reperfusion. In the patient with hepatic arterial thrombosis, the recovery of hepatic oxygenation was impaired and lactic acidosis persisted.

Intraoperative Death in Cardiac Amyloidosis with Increased QT Dispersion in the Electrocardiogram

A 22-yr-old woman on dialysis due to secondary amyloid- osis associated with rheumatoid arthritis was admitted for renal transplantation. Amyloid had also been found in the rectum, urinary bladder, spleen, and thyroid. She was short (110 cm, 45 kg) with cushingoid habitus. Her need for anti- hypertensive medication had gradually vanished. She used propranolol for palpitation and was confined to wheelchair. On admission, arterial blood pressure was 110/70 mm Hg. ECG showed sinus tachycardia 110 bpm. Chest radiograph was normal. Laboratory values were: hemoglobin 10.1 g/dL, creatinine 509 pmol/L, and potassium 4.4 mmol/L. Endo- tracheal intubation with fiberscope was difficult. Anesthesia was induced with fentanyl and propofol and maintained with fentanyl, isoflurane, nitrous oxide, and vecuronium. An arterial line was impossible to establish due to subcuta- neous fat. Central venous blood gases after induction showed: pH, 7.28, Pao, 50 mm Hg, and Pace, 46 mm Hg. The central venous pressure was maintained 5-9 mm Hg. A IO-min period with arterial pressure of 70-100/40-50 mm Hg resulted in a transient depression of the ST seg- ment in ECG. Nitroglycerine 20 pg/min and dopamine 12 pg * kg-’ * min-’ were started. Thirty minutes after reperfusion of the graft, the heart rate decreased from 60 to 40 bpm with a decrease in arterial pressure to 78/40 mm Hg. ECG showed complete atrio- ventricular block. Atropine 1 mg was given twice without response. Ventricular fibrillation 6 min later was treated with epinephrine and defibrillation resulting in short-lasting supraventricular tachycardia followed by bradycardia, This work was supported by the S&rid Juselius Foundation, Helsinki, Finland. Accepted for publication February 9, 1995. Address corr&pondence and reprint requests to Minna Tallgren, MD, Deuartment of Anaesthesia, Suraical Hospital, Kasarmikatu 11-13, 06130 Helsinki, Finland. ” *