Johan Lundberg

Increased blood-brain barrier permeability of morphine in a patient with severe brain lesions as determined by microdialysis.

Intracerebral microdialysis was utilised to obtain information regarding how morphine is transported across the blood–brain barrier (BBB). In a patient with a severe brain injury, we measured simultaneously unbound extracellular fluid (ECF) concentrations of morphine in human brain and in subcutaneous fat tissue, which were compared to morphine levels in arterial blood. This report shows an increase in morphine levels near the trauma site in the brain compared to uninjured brain tissue. The half‐life of morphine in uninjured and injured brain tissue of 178 min and 169 min, respectively, were comparable but were longer than in blood (64 min) and adipose tissue (63 min). This indicates that morphine is retained in brain tissue for a longer time than what could be expected from the blood concentration–time profile. These results show the potential of the microdialysis technique in providing new information regarding the pharmacokinetics of drug in the human brain close to the trauma site and in macroscopically intact tissue.

Preoperative ropivacaine infiltration in breast surgery

The aim of the study was to investigate whether preoperative infiltration with ropivacaine in conjunction with breast surgery improves postoperative pain management and attenuates postoperative nausea and vomiting.

Hemodynamic Effects of Dopamine during Thoracic Epidural Analgesia in Man

The cardiovascular effects of dopamine were studied before and during thoracic epidural analgesia (TEA) in eight patients prior to abdominal aortic surgery. Dopamine was infused at rates of 2, 4, and 8 micrograms X kg-1 X min-1. Mean plasma dopamine concentration increased proportionally to the infusion rate. Before TEA, dopamine 8 micrograms X kg-1 X min-1 decreased systemic vascular resistance 4 +/- 4 mmHg min X 1-1 (m +/- SD) (P less than 0.05), but increased mean arterial pressure 15 +/- 12 mmHg (P less than 0.01), cardiac output 1.9 +/- 1.0 1 X min-1 (P less than 0.01), heart rate 10 +/- 9 beats X min-1 (P less than 0.05), and plasma norepinephrine concentration 544 +/- 252 pg X ml-1 (P less than 0.01). After the induction of TEA, which extended above the T2 dermatome and below the L2 dermatome, saline and albumin were infused to maintain central venous and pulmonary capillary wedge pressures. TEA reduced mean arterial pressure from 96 +/- 18 to 55 +/- 8 mmHg (P less than 0.01), cardiac output from 4.7 +/- 0.9 to 3.9 +/- 0.9 1 X min-1 (P = 0.05), systemic vascular resistance from 21 +/- 6 to 14 +/- 3 mmHg min X 1-1 (P less than 0.05), and plasma norepinephrine concentration from 394 +/- 141 to 207 +/- 73 pg X ml-1 (P less than 0.01). The plasma epinephrine concentration was reduced 49% after the induction of TEA.(ABSTRACT TRUNCATED AT 250 WORDS)

Wound infiltration with ropivacaine and fentanyl: Effects on postoperative pain and PONV after breast surgery

STUDY OBJECTIVEnTo determine whether postoperative wound infiltration with local anesthetics combined with fentanyl improves analgesia following breast surgery; and to investigate awakening and postoperative nausea/vomiting.nnnDESIGNnProspectively randomized clinical study.nnnSETTINGnUniversity hospital.nnnPATIENTSn45 ASA physical status I and II patients scheduled for breast surgery.nnnINTERVENTIONSnPatients were prospectively randomized and assigned to one of three treatments during general anesthesia: postsurgical wound infiltration with ropivacaine 0.375%; wound infiltration with ropivacaine 0.375% combined with fentanyl 0.5 microg/kg; and intravenous (i.v.) fentanyl 0.5 microg/kg before skin incision and no wound infiltration. Time to first verbal response, pain at rest, postoperative nausea and vomiting, and ketobemidone and dixyrazine utilization were compared.nnnMEASUREMENTS AND MAIN RESULTSnTime to first verbal response was significantly shorter in the i.v. fentanyl group compared to both infiltration groups (8.1 +/- 4.5 min vs. 15.3 +/- 4.3, and 12.0 +/- 5.0 min; p < 0.05, respectively). Postoperative pain at rest, and nausea and vomiting occurred with similar frequencies in the groups. Ketobemidone utilization in both infiltration groups, (2.4 +/- 1.8 mg and 3.1 +/- 1.8 mg, respectively) was not different compared to the i.v. fentanyl group (2.9 +/- 2.0 mg; NS). There were no differences in postoperative antiemetic requirements during the first, second and third two-hour periods postoperatively. The dixyrazine consumption was similar in the three groups, (0.9 +/- 1.5 mg, 0.8 +/- 1.3 mg, and 1.4 +/- 1.8 mg, respectively; NS).nnnCONCLUSIONnPostsurgical ropivacaine wound infiltration, with or without adding fentanyl, demonstrates no differences in postoperative pain relief and nausea/vomiting compared to a balanced general anesthetic including i.v. fentanyl.

Thoracic epidural anesthesia and epidural hematoma.

This report involves a 74‐year‐old‐male who developed a thoracic epidural hematoma with paraparesis on the second postoperative day in conjunction with thoracic epidural anesthesia established before surgery for acute abdominal aortic dissection.

Morphine Metabolism After Major Liver Surgery

BACKGROUND:Impaired metabolism of morphine may lead to an increase in sedation and respiratory depression. METHODS:In the present study we investigated morphine pharmacokinetics in patients who had undergone liver resection (n = 15) compared to a control group undergoing colon resection (n = 15). Morphine was administered IV by patient-controlled analgesia. Plasma concentrations of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were measured 2–3 times daily for the first two postoperative days. Pain intensity scores were assessed three times daily and respiratory rate and sedation scores every third hour. RESULTS:There were no differences in morphine requirements 1.1 (0.8–2.5 [median, interquartile range]) mg/h (liver resection) and 1.5 (1.1–1.7) mg/h (colon resection) [P = 0.84]) or in pain intensity scores (P > 0.3) between the groups. Plasma morphine concentrations were higher in patients undergoing liver resection than in the control group (P < 0.01) reflecting a lower rate of morphine metabolism. Plasma morphine concentrations were correlated with the volume of liver resection (P < 0.02). However, plasma concentrations of morphine-6-glucuronide and morphine-3-glucuronide did not differ between the groups (P = 0.62 and P = 0.48, respectively). There was a higher incidence of sedation (P = 0.02), but not respiratory depression (P = 0.48), after liver resection. CONCLUSION:The study demonstrates that plasma concentrations of morphine are higher in patients undergoing liver resection compared with patients undergoing colon resection. Sedation scores were higher in patients undergoing liver resection. Caution is therefore recommended when administering morphine to this patient group.

Cardiovascular depression by isoflurane and concomitant thoracic epidural anesthesia is reversed by dopamine

Interactive effects between exogenous dopamine (DA) and isoflurane (I) combined with thoracic epidural blockade (TEA) were studied in dogs during chloralose anesthesia. The I–TEA intervention per se decreased heart rate (HR; 28%), mean arterial pressure (MAP; 63%), cardiac output (CO; 54%), left ventricular dP/ dt (LVdP/dt; 75%) and LVdP/dt/systolic arterial pressure (SAP; 42%). Prior to the I–TEA intervention, dopamine increased MAP, CO, LVdP/dt, LVdP/dt/SAP and stroke volume (SV) already at the dose 10 μg–kg‐1. min‐1 and, additionally, increased mean pulmonary artery pressure (MPAP) at the dose 20 μg–kg‐1. min‐1. During the I–TEA intervention, the DA–induced increases in MAP and systemic vascular resistance (SVR) were significantly higher than prior to I–TEA, as indicated by significant ANOVA interactive effects. At the dose 10 μg–kg‐1 min‐1, DA restored MAP, CO, LVdP/dt, LVdP/dt/SAP and SV to levels found before the I–TEA intervention, while HR was restored first at the dose 20 μg–kg‐1 –min‐1. At the dose 20 μg–kg‐1–min‐1, DA also increased MAP (39%), LVdP/dt (119%), LVdP/dt/SAP (73%), SVR (28%) and MPAP (70%) above levels prior to I–TEA. To conclude, exogenous dopamine effectively and dose–dependently counters cardiovascular depression induced by the anesthetic technique of combining I and TEA. The pressor and systemic vasoconstrictor actions of dopamine are potentiated by conjoint administration of I and TEA.

Effects of thoracic epidural anesthesia and adrenoceptor blockade on the cardiovascular response to dopamine in the dog

The cardiovascular effects of dopamine are different before and during thoracic epidural anesthesia (TEA). To evaluate underlying adrenoceptor‐mediated mechanisms, dopamine effects were investigated in nine chloralose‐anesthetized dogs. The circulatory response to dopamine (0–40 μg · kg‐1 · min‐1) was studied before and during TEA, and during TEA after introducing the α1‐antagonist prazosin (0.3 mg · kg‐1), the α2‐antagonist rauwolscine (0.3 mg · kg‐1), and the β1‐antagonist metoprolol (0.5 mg · kg‐1). TEA decreased mean arterial pressure (MAP) by 29%, cardiac output (CO) by 36%, heart rate (HR) by 27%, and the maximum rate of change of left ventricular pressure (LVdP/dt) by 52%. Systemic vascular resistance, pulmonary vascular resistance and mean pulmonary artery pressure (MPAP) remained unaltered by TEA. Dopamine‐induced increases in MAP and HR were augmented by TEA. Both MAP and LVdP/dt increased above pre‐TEA levels at 10 μg · kg‐1 · min‐1. Prazosin attenuated the increases in MAP and MPAP by dopamine. Adding rauwolscine almost abolished the dopamine response in MAP and MPAP. Metoprolol almost eliminated the dopamine effects on CO and LVdP/dt. Only minor alterations in cardiac filling pressures were observed during the study. Plasma norepinephrine (NE) concentration was lower during than before TEA at corresponding dopamine infusion rates. NE was reduced by the β1‐blockade. During TEA, the plasma dopamine levels were generally higher, and they were further increased by adding β1‐blockade. In conclusion, myocardial contractility and arterial pressure were restored to pre‐TEA values by dopamine at 5–10 μg · kg‐1 · min‐1. The circulatory response to dopamine during TEA is mainly mediated by α1‐, α2‐ and β1‐adrenoceptor activation, and may be influenced by altered plasma catecholamine levels.

Apnea and bradypnea in patients receiving epidural bupivacaine-morphine for postoperative pain relief as assessed by a new monitoring method.

STUDY OBJECTIVEnTo evaluate postoperative breathing patterns with a new monitoring device in patients given bupivacaine-morphine epidural analgesia.nnnDESIGNnOpen explorative study.nnnSETTINGnInpatient anesthesia in a university hospital setting.nnnPATIENTSn15 ASA physical status I and II patients aged 28 to 87 years and scheduled for major abdominal surgery.nnnINTERVENTIONSnAll patients underwent abdominal surgery with epidural anesthesia combined with general anesthesia. Postoperatively, they continued with epidural analgesia consisting of bupivacaine and morphine. On the first postoperative night, the breathing pattern was studied with a new noninvasive monitoring device measuring respiratory frequency and apnea. Arterial blood gas analysis was performed in case of apnea or low respiratory frequency.nnnMEASUREMENTS AND MAIN RESULTSnA total of 84 alarm events were registered in 11 patients. Twenty-one percent (18/84) of the alarms were associated with arterial carbon dioxide tension (PaCO2) levels greater than 48.8 mmHg. Three of the four patients with PaCO2 levels greater than 48.8 mmHg were older than 80 years of age.nnnCONCLUSIONnThe tested noninvasive monitoring device may detect abnormal respiratory breathing patterns in patients at risk for respiratory depression during epidural analgesia with bupivacaine-morphine.

Local metabolic changes in subcutaneous adipose tissue during intravenous and epidural analgesia

Background: This clinical study aimed at investigating the impact of postoperative thoracic epidural analgesia on extracellular glycerol concentration and glucose metabolism in subcutaneous adipose tissue, using the microdialysis technique. The sympathetic nervous activity, which can be attenuated by epidural anesthesia, influences lipolysis and the release of glycerol.