Reino Pöyhiä

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.

Medical undergraduate students’ beliefs and attitudes toward pain – How do they mature?

At the University of Helsinki, pain‐related topics are taught throughout medical studies but without a formal pain curriculum. The purpose of this study was to assess medical students’ attitudes towards pain.

Serum Cystatin C in Elderly Cardiac Surgery Patients

BACKGROUND Elderly cardiac surgery patients are more prone to develop postoperative acute kidney injury (AKI). The common clinical glomerular filtration marker, plasma creatinine, is considered to be inadequate to discover AKI in its early stage. The aim of this study was to determine if serum cystatin C can detect mild renal failure earlier than plasma creatinine. METHODS From 110 cardiac surgery patients aged 70 or greater years, serum cystatin C and plasma creatinine samples were collected preoperatively and on postoperative days 1 to 5. Their urine output, creatinine, and estimated glomerular filtration rate were calculated and AKI was determined by the risk-injury-failure-loss-end-stage kidney disease criteria (RIFLE). The correlation of plasma creatinine and serum cystatin C to AKI was calculated. RESULTS After cardiac surgery, 62 of the 110 patients (56.4%) developed AKI according to the RIFLE classification. In this group, both serum cystatin C and plasma creatinine peaked on postoperative day 3. Cystatin C and creatinine correlated equally with AKI at different time points calculated with receiver operating characteristic curves. On postoperative day 1 the area under the curve (AUC) for creatinine was 0.66 (0.55 to 0.76) and for cystatin C 0.71 (0.61 to 0.81); Delta AUC 0.05 (0.01 to 0.12), p = 0.11. On postoperative day 2 the AUC for creatinine was 0.74 (0.64 to 0.83) and for cystatin was C 0.77 (0.68 to 0.86); Delta AUC -0.03 (-0.09 to 0.03), p = 0.32. CONCLUSIONS Elderly cardiac surgery patients have a high incidence of AKI, as defined by the RIFLE criteria. After cardiac surgery serum cystatin C and plasma creatinine detected AKI similarly.

The effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm

N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but in experimental studies it has been shown to impair coagulation. Since very little is known about the effects of NAC on blood coagulation in surgical patients, we studied its effects during abdominal aortic reconstruction. NAC (a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the same volume of placebo was given intravenously, in a randomized double-blinded fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet aggregation were studied during and after surgery. Total blood loss was also measured. The median (25th–75th percentiles) decrease of the prothrombin time value was 33.0% (30–37%) after NAC treatment and 6.5% (4–8%) after placebo (P < 0.001). Postoperative prothrombin time values remained lower in the patients receiving NAC. In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC (P = 0.02). Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin time values before and after bolus infusions were associated with increased blood loss (P = 0.008 and P = 0.015, respectively). NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery. This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk.

Patient-controlled sedation with propofol and remifentanil for ERCP: a randomized, controlled study

BACKGROUND Deep sedation with propofol and an opioid is commonly used for ERCP but is associated with increased risk and may require the presence of an anesthesiologist. Delivery of propofol and a short-acting, potent opioid analgesic remifentanil by patients to themselves (patient-controlled sedation, PCS) could be another option. Comparative studies with propofol PCS for ERCP are lacking. OBJECTIVE To compare PCS with propofol/remifentanil to anesthesiologist-managed propofol sedation. DESIGN Prospective, randomized, controlled human trial. SETTING University hospital. PATIENTS This study involved 80 patients presenting for elective ERCP. INTERVENTION Patients were randomized to PCS with propofol/remifentanil (PCS group) or anesthesiologist-managed propofol sedation (propofol infusion group). Sedation level was estimated every 5 minutes throughout the procedure by using Ramsay and Gillham sedation scores. The total amount of propofol was calculated at the end of the procedure. Endoscopist and patient satisfaction with the procedures was evaluated with a structured questionnaire. MAIN OUTCOME MEASUREMENTS Patient vital signs, amount of consumed propofol, sedation levels, and degree of endoscopist and patient satisfaction. RESULTS PCS was successful with 38 of 40 (95%) ERCP patients. In the PCS group, the mean (±standard deviation) level of sedation was markedly lighter and propofol consumption significantly smaller (175±98 mg) than in the propofol infusion group (249±138 mg) (P<.01). Degrees of patient and endoscopist satisfaction were equally high in both groups. All of the patients preferred the same sedation method should a repeat ERCP be required. LIMITATIONS Single-center study. CONCLUSION PCS with propofol/remifentanil is a suitable and well-accepted sedation method for ERCP. Anesthesiologist-managed propofol sedation with constant propofol infusion is associated with unnecessary deep sedation without any impact on the degree of patient or endoscopist satisfaction. Further larger-scale studies are needed to assess the safety of PCS in ERCP patients. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01079312.).

Autologous bone marrow mononuclear cell transplantation in ischemic heart failure: A prospective, controlled, randomized, double-blind study of cell transplantation combined with coronary bypass

BACKGROUND Bone marrow mononuclear cell (BMMC) transplantation for heart failure has shown inconsistent therapeutic efficacy. METHODS We enrolled 104 ischemic heart failure patients scheduled for coronary artery bypass surgery (CABG). After 4- to 12-week pharmacotherapy optimization, 39 patients with left ventricular ejection fraction (LVEF) of ≤45% received injections of BMMC or vehicle intra-operatively into the myocardial infarction border area in a randomized, double-blind manner. RESULTS The median number of cells injected was 8.4 × 10(8) (interquartile range [IQR]: 5.2 × 10(8) to 13.5 × 10(8)). We measured LV function and myocardial scar size by magnetic resonance imaging (MRI), and viability by positron emission tomography (PET) and single-photon emission computed tomography (SPECT), pre-operatively and after 1-year follow-up. LVEF, the pre-defined primary end-point measure, improved by a median of 5.6% in the control group (IQR 0.2 to 10.1) and by 4.8% in the BMMC group (IQR -0.5 to 8.2) (p = 0.59). Wall thickening in injected segments rose by a median of 4.5% among controls (IQR -18.1 to 23.9) and by 5.5% in the BMMC group (IQR -6.6 to 26.5) (p = 0.68). Changes in viability by PET and SPECT did not differ between groups. Myocardial scar size by MRI in injected segments rose by a median of 5.1% among controls (IQR -3.3 to 10.8), but fell by 13.1% in the BMMC group (IQR -21.4 to -6.5) (p = 0.0002). CONCLUSIONS BMMC therapy combined with CABG failed to improve LV systolic function, or viability, despite reducing myocardial scar size.

Patient-controlled sedation for ERCP: a randomized double-blind comparison of alfentanil and remifentanil.

BACKGROUND AND STUDY AIMS Self-administration of a propofol and opioid mixture by patients (patient-controlled sedation, PCS) could offer a practical alternative for individual sedation during endoscopic retrograde cholangiopancreatography (ERCP). However, what would be the most suitable sedative mixture for PCS is unknown. The aim of this study was to compare remifentanil and alfentanil in the PCS during ERCP. PATIENTS AND METHODS Eighty-one patients undergoing elective ERCP received PCS with propofol and opioid in three different regimens. The concentrations of opioids in the sedative mixture were 0.02 mg/mL in the remifentanil group (R) and 0.04 mg/mL and 0.08 mg/mL in the alfentanil 1 (A1) and alfentanil 2 (A2) groups, respectively. The infusion pump was adjusted to deliver a 1 mL single dose with zero lockout time. We considered PCS as successful if no procedure interruption due to sedation-related complications occurred or if additional propofol was not needed. The consumption of propofol was registered, and sedation levels and vital signs were monitored. Endoscopist and patient satisfaction with sedation were assessed using structured questionnaires. RESULTS The consumption (SD) of propofol was 177 (105)mg in group R, 197 (88) mg in group A1 and 162 (70)mg in group A2. PCS was successful in 74 /81 (91 %) of sedations, without differences between the groups in terms of propofol consumption, sedation success rate, sedation levels, vital signs, postprocedural pain, and endoscopist and patient satisfaction. Respiratory depression and nausea were observed more frequently with remifentanil than with alfentanil (P < 0.05). CONCLUSIONS PCS is an acceptable method of sedation for ERCP. The combination of propofol and alfentanil should be recommended because a remifentanil - propofol mixture depresses spontaneous respiration more and produces nausea more frequently.

Systemic physostigmine shows antiallodynic effects in neuropathic rats.

UNLABELLED The aim of this study was to examine the antiallodynic and antinociceptive effects of subcutaneously administered physostigmine (50, 100, 200 micrograms/kg), compared with morphine (2.5, 5, 10 mg/kg) and NaCl after spinal nerve ligation in rats. The following stimuli were used: acetone (cold allodynia), von Frey hairs (mechanical allodynia), and paw flick test (thermal nociception). Motility boxes were used to investigate the effects of the drugs on motor performance. Physostigmine attenuated both mechanical and cold allodynia dose-dependently but had no effect on the paw flick test. The effect was antagonized by atropine (muscarinic receptor antagonist) but not by mecamylamine (nicotinic receptor antagonist) or naloxone (opioid receptor antagonist). Morphine produced dose-dependent antiallodynic and antinociceptive effects. In the antiallodynic doses, morphine caused severe rigidity. Physostigmine 200 micrograms/kg impaired locomotor activity, but no rigidity was observed. IMPLICATIONS Physostigmine has different effects on allodynia and nociception, which suggests that different cholinergic (muscarinic) mechanisms may be involved in neuropathic and nociceptive pain.

A randomized comparison of target-controlled propofol infusion and patient-controlled sedation during ERCP

BACKGROUND AND STUDY AIMS Propofol is widely used during endoscopic retrograde cholangiopancreatography (ERCP) but high doses are recognized as a risk factor for sedation-related complications. The aim of this study was to compare target-controlled infusion (TCI) with patient self-administration (patient-controlled sedation, PCS) of propofol during ERCP. Propofol consumption, the ease of ERCP performance, and speed of recovery were recorded. PATIENTS AND METHODS A total of 82 patients undergoing elective ERCP were randomized 1:1 to receive propofol 10 mg/mL using TCI (initial targeted effect-site concentration 2 μg/mL) or PCS (single bolus 1 mL, lockout time set at zero). Alfentanil was administered if signs of insufficient analgesia occurred. Consumption of propofol and alfentanil was recorded, sedation levels and vital signs were monitored, the ease of ERCP performance, speed of recovery, and satisfaction with sedation were evaluated. RESULTS All procedures were performed without interruptions or major sedation-related complications. The mean (± SD) consumption of propofol was 306 ± 124 mg in the TCI group and 224 ± 101 mg in the PCS group (P = 0.002). Patients in the PCS group recovered faster (P = 0.035). The mean (± SD) consumption of alfentanil was 0.5 ± 0.4 mg in both groups. The combination of propofol and alfentanil was associated with an increased risk of sedation-related adverse events (P = 0.031). CONCLUSIONS No benefits of TCI over PCS could be demonstrated in this study. We recommend considering PCS as a feasible option for propofol administration during ERCP because of its ease of use, high success rate, reduced consumption of propofol, and faster recovery.

Effects of levosimendan on renal function in patients undergoing coronary artery surgery.

OBJECTIVES To evaluate the effect of levosimendan on postoperative renal function in patients with compromised heart function undergoing on-pump coronary artery bypass graft surgery. DESIGN A prospective, randomized, placebo-controlled, double-blind substudy. SETTING Cardiothoracic surgery, anesthesiology, and intensive care units at 2 university hospitals. PARTICIPANTS Sixty patients with left ventricular ejection fraction ≤50% were randomized into 2 parallel treatment groups. INTERVENTIONS Levosimendan or placebo was started after the induction of anesthesia with a 12-μg/kg bolus in 10 minutes followed by the infusion of 0.2 μg/kg/min for the next 23 hours and 50 minutes. MEASUREMENTS AND RESULTS Serum cystatin C and plasma creatinine were measured at baseline; at 6 and 24 hours after declamping the aorta; and on the 1st, 2nd, and 5th postoperative days. Urine N-acetyl-β-glucosaminidase (U-NAG) was measured at baseline and at 6 and 24 hours after declamping of the aorta. Renal function was estimated with calculated glomerular filtration rate (eGFR). The changes in plasma creatinine, serum cystatin C, and urine NAG were not significant among the placebo and the levosimendan groups at any of the measuring points. CONCLUSIONS After coronary artery surgery, levosimendan did not have a significant influence on the kidney function measured with these specific kidney markers.