Timo Salomäki

BOLD-contrast functional MRI signal changes related to intermittent rhythmic delta activity in EEG during voluntary hyperventilation—simultaneous EEG and fMRI study

Differences in the blood oxygen level dependent (BOLD) signal changes were studied during voluntary hyperventilation (HV) between young healthy volunteer groups, (1) with intermittent rhythmic delta activity (IRDA) (N = 4) and (2) controls (N = 4) with only diffuse arrhythmic slowing in EEG (normal response). Subjects hyperventilated (3 min) during an 8-min functional MRI in a 1.5-T scanner, with simultaneous recording of EEG (successful with N = 3 in both groups) and physiological parameters. IRDA power and average BOLD signal intensities (of selected brain regions) were calculated. Hypocapnia showed a tendency to be slightly lighter in the controls than in the IRDA group. IRDA power increased during the last minute of HV and ended 10-15 s after HV. The BOLD signal decreased in white and gray matter after the onset of HV and returned to the baseline within 2 min after HV. The BOLD signal in gray matter decreased approximately 30% more in subjects with IRDA than in controls, during the first 2 min of HV. This difference disappeared (in three subjects out of four) during IRDA in EEG. BOLD signal changes seem to depict changes, which precede IRDA. IRDA due to HV in healthy volunteers represent a model with a clearly defined EEG pattern and an observable BOLD signal change.

Improving the quality of postoperative pain relief

A review of the literature shows a constant need to improve the quality of postoperative pain management. The objective of this study was to decrease the intensity and variation of postoperative pain by developing a nurse‐based pain service on the ward. An acute pain nurse was appointed and an educational programme with detailed algorithms was started. Regular pain intensity measurements were implemented. Postoperative pain intensity, treatments and side‐effects were assessed both before and after the introduction of the new system in 400 patients divided into two consecutive groups of equal size. The number of patients with inadequately treated pain (actual pain > 3/10) dropped by 64% after major gynaecological surgery (25 vs 9%, 95% CI for differences 7–24%;p< 0.001 for pain scores). On an average, inadequate pain relief (retrospective average pain > 3/10) on the first postoperative day was more frequent on the ward before than after the reform (47 vs 21%; 95% CI for differences 15–35%;p< 0.001 for pain scores). The incidence of side‐effects was similar in both groups (p> 0.05). The intensity and variation of postoperative pain on the ward decreased by developing a nurse‐based pain service with an acute pain nurse, an educational programme and regular pain intensity measurements.

Ph-stat versus alpha-stat perfusion strategy during experimental hypothermic circulatory arrest: a microdialysis study

BACKGROUND The superiority of the pH-stat to the alpha-stat acid-base strategy during cardiopulmonary bypass as a neuroprotective method during hypothermic circulatory arrest is still controversial. In the present study, brain metabolism and outcome have been evaluated in a surviving model of experimental hypothermic circulatory arrest. METHODS Twenty pigs undergoing 75-minutes of hypothermic circulatory arrest at a brain temperature of 18 degrees C were randomly assigned to the alpha-stat (n = 10) or pH-stat (n = 10) strategy during cardiopulmonary bypass. RESULTS The 7-day survival rate was 90% (9 of 10) in the pH-stat group and 10% (1 of 10) in the alpha-stat group. At the end of cooling, pH-stat strategy was associated with significantly lower brain lactate and pyruvate concentrations and brain lactate-glucose ratio. After reperfusion, brain concentrations of glycerol, lactate, pyruvate, and lactate-glucose ratio were significantly lower in the pH-stat group. This strategy was associated with a faster rise of brain tissue temperature and reoxygenation on reperfusion, which is likely secondary to improved cerebral perfusion. CONCLUSIONS During cardiopulmonary bypass before and after a period of hypothermic circulatory arrest, acid-base management according to the pH-stat principles seemed to be associated with less derangements in cerebral metabolism, lower intracranial pressures, and excellent behavioral recovery and survival outcome. Because there is strong evidence of the beneficial metabolic effects related to this method, further studies using an experimental model of combined HCA and embolic brain injury are required to exclude a possible increased risk of cerebral embolism associated with the pH-stat strategy.

Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.

BACKGROUND Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury. METHODS Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups. RESULTS There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate levels (P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA (P = .049). CONCLUSION The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.

Successful Resuscitation after Cardiovascular Collapse following Accidental Intravenous Infusion of Levobupivacaine during General Anesthesia

A 63-yr-old, 77-kg man with localized prostate cancer but no other medical history presented for brachytherapy. The patient was premedicated with 10 mg oral diazepam and 1 g oral paracetamol 60 min before anesthesia. At the time of arrival in the operating room, saline infusion was started, and the monitors were connected: five-lead electrocardiogram, end-tidal carbon dioxide, end-tidal sevoflurane concentration, noninvasive arterial blood pressure, pulse oximetry, Entropy index (GE Health Care Finland, Helsinki, Finland), and peripheral nerve stimulator. For prophylaxis, infusion of 200 mg ciprofloxacin (100 ml) was started 5 min before the induction of anesthesia. General anesthesia was induced with thiopental (425 mg), fentanyl (0.1 mg), and rocuronium (50 mg). Tracheal intubation was performed, and controlled ventilation was started (40% oxygen in air with 1.1–1.7% sevoflurane). The patient’s arterial blood pressure and heart rate were 152/95 mmHg and 75 beats/ min, respectively, initially, and 125/85 mmHg and 70 beats/min 5 min after induction. Ten minutes after induction (15 min after the initiation of antibiotic infusion), arterial blood pressure was 85/60 mmHg, heart rate was 60 beats/min, and end-tidal carbon dioxide was 32 mmHg. To increase arterial blood pressure, the patient was given 1 mg intravenous etilefrine. Five minutes later, when the infusion of the prescribed antibiotic dose (100 ml) was completed (during the past 20 min), it was noticed that the administered infusion was not antibiotic but 125 mg levobupivacaine (Chirocain; Abbot, Espoo, Finland). The levobupivacaine, which was intended for epidural infusion, was packed in a similar 100-ml plastic infusion bag as the antibiotic. At the same time, arterial blood pressure was not measurable noninvasively, and there was no pulse in the left radial artery. Electrocardiogram showed a heart rate of 55 beats/min, and there were no changes in ST level or rhythm. There were no changes in the Entropy indexes or end-tidal carbon dioxide (32 mmHg), either. The patient was immediately given 0.2 mg intravenous epinephrine, and his arterial blood pressure increased to 85/65 mmHg. His left radial artery was cannulated, blood gas analysis was performed, and the oxygen fraction in the ventilator was increased to 100%. His blood gas values were as follows: pH, 7.37; partial pressure of carbon dioxide, 45 mmHg; base excess, 0.9 mmHg; partial pressure of oxygen, 187 mmHg. Seven minutes later, arterial blood pressure decreased again, to 62/45 mmHg, and 0.1 mg epinephrine was given intravenously. Arterial blood pressure then increased to 95/55 mmHg, and the infusion of norepinephrine was started. Norepinephrine was infused during the first 5 min at a dose of 0.17 g kg 1 min 1 and thereafter at 0.09 g kg 1 min 1 over the next 70 min until the end of anesthesia. When systolic blood pressure stabilized at the level of 95–100 mmHg after starting the norepinephrine infusion, the surgical procedure was performed. During this period, there were numerous extra supraventricular beats, multiple transitory changes in ST levels, and short periods of nodal rhythm. After the operation, the patient awakened normally, and he was kept in the recovery room overnight for monitoring. There were no changes in his postoperative electrocardiogram, and his glucose, electrolyte, and troponin plasma concentrations were normal. The arterial levobupivacaine concentrations were 1.74 mg/l at 40 min (after starting the infusion of levobupivacaine), 0.81 mg/l at 100 min, and 0.60 mg/l at 160 min. The patient had no sequelae, and he was informed about the accidental infusion. A thorough investigation was performed in the department to find out how this accident had been possible and how a similar instance could be prevented in the future. The pharmaceutical company (Abbot) was also informed of the fact that their epidural 0.125% levobupivacaine (100 ml) was packaged similarly to some intravenous antibiotics.

Propofol is Associated with Impaired Brain Metabolism during Hypothermic Circulatory Arrest: An Experimental Microdialysis Study

BACKGROUND Propofol is a widely used anesthetic in cardiac surgery. It has been shown to increase cerebrovascular resistance resulting in decreased cerebral blood flow. Efficient brain perfusion and tissue oxygenation during cardiopulmonary bypass (CPB) is essential in surgery requiring hypothermic circulatory arrest (HCA). The effects of propofol on brain metabolism are reported in a surviving porcine model of HCA. METHODS Twenty female juvenile pigs undergoing 75 minutes of HCA at a brain temperature of 18 degrees C were assigned to either propofol- or isoflurane anesthesia combined with alpha-stat perfusion strategy during CPB cooling and rewarming. Brain microdialysis analysis was used for determination of brain metabolism, and tissue oxygen partial pressure and intracranial pressures were also followed-up until 8 hours postoperatively. RESULTS Brain concentrations of glutamate and glycerol were significantly higher in the propofol group throughout the experiment (P < .01 and P < .01, respectively). The lactate/pyruvate ratio was significantly higher in the propofol group at 6-, 7-, and 8-hour intervals (P < .05, P < .01, and P < .05, respectively). The intracranial pressure was significantly higher at the 8-hour postoperative interval (P < .05) in the propofol group. A trend toward higher brain oxygen concentrations was observed in the isoflurane group. CONCLUSIONS Anesthesia with propofol as compared with isoflurane is associated with impaired brain metabolism during experimental HCA.

EEG burst recovery is predictive of brain injury after experimental hypothermic circulatory arrest

Objective--To evaluate whether electroencephalography (EEG) recovery could be considered a reliable marker of brain injury after experimental hypothermic circulatory arrest (HCA). Design--Cortical electrical activity was registered before and after a 75-min period of HCA in 27 pigs that survived 7 days after the experiment. The sum of EEG bursts was counted as a percentage of the sum of artifact-free bursts and suppressions, and this percentage was used as a measure of EEG activity in the analysis. Results--Brain infarction developed in 13 animals (48.1%), in 12 cases (44.4%) having involved the cortex, in 1 case the thalamus (3.7%) and in another the hippocampus (3.7%). The mean EEG burst percentage significantly correlated with the total brain histopathological score (ρ = −0.588, P = 0.001). EEG burst percentage from the 2 h 20 min to the 7 h 20 min interval correlated with the total brain histopathological score and with the cortex, brainstem and cerebellum scores. The mean EEG burst percentage rate was higher, but not significantly, among the animals without brain infarction (38.5% vs 32.4%), but such a difference was significant at the 3 h 20 min postoperative interval (P = 0.02). The mean EEG burst percentage significantly correlated with brain glucose concentration at the 1 h interval (ρ = 0.387; P = 0.046), brain lactate concentration at the 2 h interval (ρ = −0.431; P = 0.025), and the brain lactate/glucose ratio at the 1 h 30 min interval from the start of rewarming (ρ = −0.433; P = 0.024). Conclusion--A decreased EEG burst percentage seems to be associated with an increased risk of developing histologically evident brain ischemic injury in the cortex, brainstem and cerebellum after experimental HCA.

Apotransferrin, C1‐esterase inhibitor, and alpha 1‐acid glycoprotein for cerebral protection during experimental hypothermic circulatory arrest

Background—Because of current limitations in improving metabolic support to the brain during hypothermic circulatory arrest (HCA), attenuation of ischemia‐reperfusion injury remains an area of therapeutic intervention of relevance. Apotransferrin (Apo‐Tf), alpha 1‐acid glycoprotein (AGP), and C1‐esterase inhibitor (C1‐INH) have been herein evaluated as potential beneficial agents in reducing the ischemia‐reperfusion injury in a surviving model of HCA. Methods—Apo‐Tf 100 mg/kg (n = 6), C1‐INH 50 IU/kg (n = 6), AGP 100 mg/kg (n = 6), or NaCl 0.9% 2 ml/kg (n = 6) were randomly administered to 24 juvenile pigs after a 75‐min period HCA at a brain temperature of 18°C. Results—Animals in the Apo‐Tf group had a slightly better 7‐day survival (66.7%) compared with the other study groups (50%), but such a difference was not statistically significant. Some favorable changes in the brain glucose metabolism parameters were observed in the AGP, C1‐INH, and Apo‐Tf groups, but these did not reach statistical significance. Semiquantitative analysis of the histopathological findings did not show any significant difference between the study groups. However, only two out of four surviving animals in the Apo‐Tf group developed brain infarction, whereas all three survivors of the remaining study groups developed brain infarction. Conclusions—Although the small size of the study groups may affect the present findings, none of the metabolic and hemodynamic parameters as well as outcome endpoints indicate a substantial therapeutic efficacy of Apo‐Tf, AGP, and C1‐INH as neuroprotective agents after experimental HCA.

Aprotinin to improve cerebral outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND Aprotinin is a serine protease inhibitor, which is usually used during cardiac surgery to reduce blood loss. There is evidence that aprotinin has neuroprotective effects during ischemia. We planned this study to evaluate its potential neuroprotective efficacy during hypothermic circulatory arrest (HCA). METHODS Twenty piglets with a median weight of 25.7 kg (interquartile range, 23.9-26.6) were randomly assigned to receive aprotinin or placebo prior to a 75-minute period of HCA at 18 degrees C. Brain microdialysis parameters and neurological and histological scores were the primary outcome measures. RESULTS Changes in brain metabolic parameters and histopathological findings were favorable in the aprotinin group. Brain lactate concentrations were significantly lower in the aprotinin group during the experiment (P = .02) along with blood lactate concentrations in the aprotinin group (P = .023). Brain glucose was significantly higher during the experiment (P = 0.02). Intracranial pressure tended to be higher in the control group. Two of 10 animals in the aprotinin group and 4 of 10 in the control group failed to reach full recovery on the seventh postoperative day. Four animals of 10 in the aprotinin group and 6 animals of 10 in the control group had brain infarction (P = .40). CONCLUSIONS The present data suggest that aprotinin mitigates cerebral damage and improves neurological outcome following a period of HCA.