Awake craniotomy does not lead to increased psychological complaints.

BACKGROUND: Patients with brain tumours are increasingly treated by using the awake craniotomy technique. Some patients may experience anxiety when subjected to brain surgery while being fully conscious. However, there has been only limited research into the extent to which such surgeries actually result in anxiety or other psychological complaints. Previous research suggests that undergoing awake craniotomy surgery does not lead to psychological complaints, and that post-traumatic stress disorders (PTSD) are uncommon following this type of surgery. It must be noted, however, that many of these studies used small random samples. METHOD: In the current study, 62 adult patients completed questionnaires to identify the degree to which they experienced anxiety, depressive and post-traumatic stress complaints following awake craniotomy using an awake-awake-awake procedure. All patients were cognitively monitored and received coaching by a clinical neuropsychologist during the surgery. RESULTS: In our sample, 21% of the patients reported pre-operative anxiety. Four weeks after surgery, 19% of the patients reported such complaints, and 24% of the patients reported anxiety complaints after 3 months. Depressive complaints were present in 17% (pre-operative), 15% (4 weeks post-operative) and 24% (3 months post-operative) of the patients. Although there were some intra-individual changes (improvement or deterioration) in the psychological complaints over time, on group-level postoperative levels of psychological complaints were not increased relative to the preoperative level of complaints. The severity of post-operative PTSD-related complaints were rarely suggestive of a PTSD. Moreover, these complaints were seldom attributed to the surgery itself, but appeared to be more related to the discovery of the tumour and the postoperative neuropathological diagnosis. CONCLUSIONS: The results of the present study do not indicate that undergoing awake craniotomy is associated with increased psychological complaints. Nevertheless, psychological complaints may well exist as a result of other factors. Consequently, monitoring the patient's mental wellbeing and offering psychological support where necessary remain important.

Automated reminders decrease postoperative nausea and vomiting incidence in a general surgical population.

BACKGROUND: Guidelines to minimize the incidence of postoperative nausea and vomiting (PONV) have been implemented in many hospitals. In previous studies, we have demonstrated that guideline adherence is suboptimal and can be improved using decision support (DS). In this study, we investigate whether DS improves patient outcome through improving physician behaviour. METHODS: Medical information of surgical patients is routinely entered in our anaesthesia information management system (AIMS), which includes automated reminders for PONV management based on the simplified risk score by Apfel and colleagues. This study included consecutive adult patients undergoing general anaesthesia for elective non-cardiac surgery who were treated according to the normal clinical routine. The presence of PONV was recorded in the AIMS both during the recovery period and at 24 h. Two periods were studied: one without the use of DS (control period) and one with the use of DS (support period). DS consisted of reminders on PONV both in the preoperative screening clinic and at the time of anaesthesia. RESULTS: In the control period, 981 patients, of whom 378 (29%) were high-risk patients, received general anaesthesia. Overall, 264 (27%) patients experienced PONV within 24 h. In the support period, 1681 patients, of whom 525 (32%) had a high risk for PONV, received general anaesthesia. In this period, only 378 (23%) patients experienced PONV within 24 h after operation. This difference is statistically significant (P=0.01). CONCLUSION: Automated reminders can improve patient outcome by improving guideline adherence.

Inadvertent epidural administration of insulin.

A 67-year-old female with insulin-dependent diabetes mellitus underwent an uncomplicated partial liver resection under combined epidural and general anaesthesia. After surgery, 50 U of insulin were accidentally infused into her epidural space over a period of 5 h in addition to her prescribed intravenous insulin infusion. After recognition of the accidental epidural administration, the patient was closely monitored for any neurological signs or symptoms. Blood glucose levels decreased significantly from 17.4 to 6.8 mmol.l(-1) over a period of 7 h. Despite the hazard of potentially neurotoxic preservatives in the insulin preparation, she suffered no neurological sequelae and made an uncomplicated recovery.

Varicella zoster virus serostatus before and after kidney transplantation, and vaccination of adult kidney transplant candidates.

In recent years we observed 3 lethal primary varicella infections in adult kidney transplant recipients. Therefore, we wondered how many of our adult renal transplant patients were not protected against varicella zoster virus (VZV), and therefore were at risk for such a primary infection. We also studied the prevalence of VZV seronegativity in the adult patients on our waitlist for kidney transplantation. Finally, we vaccinated these seronegative patients with an attenuated live vaccine. Sera were obtained from 854 transplanted patients, and from 286 candidates on the waitlist for kidney transplantation. We observed that 2.1% of our renal transplant recipients and 3.2% of the patients on the waitlist were seronegative for VZV. We vaccinated 11 seronegative patients on the waitlist twice without side effects. In 7 of 11 patients this resulted in a positive serologic response. In conclusion, the prevalence of VZV seronegativity was low both in renal transplant recipients (2%) and in patients on the waitlist (3%). Vaccination of transplant candidates resulted in a moderate efficiency of 64%.

Treatment of neuropathic cancer pain with continuous intrathecal administration of S +-ketamine.

The effective treatment of patients suffering from neuropathic cancer pain remains a clinical challenge. When patients experience either insufficient analgesia or problematic side-effects after opioid administration, intrathecal administration of morphine and other medications such as bupivacaine and clonidine may offer significant advantages. Additionally, ketamine, a non-competitive N-methyl-D-Aspartate-receptor antagonist is able to alter pain perception at the spinal level. Because of the potential neurotoxicity after neuraxial use of racemic ketamine, intrathecal administration of the preservative-free active compound, S (+)-ketamine may be a valuable alternative. In this paper, we present a patient with severe neuropathic cancer pain successfully treated by continuous intrathecal infusion of morphine, bupivacaine, clonidine and S (+)-ketamine. Moreover, quality of life measurements before and 3 weeks after the start of spinal treatment revealed an improvement in pain relief and a higher overall quality of life. No clinical signs of neurologic deficit were observed during spinal treatment with S (+)-ketamine. However, the continuous intrathecal administration of S (+)-ketamine should be considered as the last resort because there are no preclinical safety data with relevant concentrations on intrathecal use of S (+)-ketamine.

Metabolic coronary-flow regulation and exogenous nitric oxide in human coronary artery disease: assessment by intravenous administration of nitroglycerin.

We sought to evaluate the effect of intravenous administration of the nitric oxide--donor substance nitroglycerin (NTG) on metabolic coronary-flow regulation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen supply and consumption (MVO2) at sinus rhythm and during atrial pacing (30 beats/min above sinus rate), both at control and during infusion of NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min. To study metabolic coronary vasodilation, changes in myocardial oxygen supply were related to pacing-induced changes in MVO2, by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control, characterizing physiological metabolic coronary flow regulation) was compared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min, attenuated pacing-induced increases in MVO2 by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/demand ratio of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 microg/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 microg/kg/min, this ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p<0.01). Intravenous administration of high-dose NTG, a donor of exogenous NO, blunts pacing-induced increases in MVO2 and may increase metabolic coronary vasodilation in patients with CAD.

A critical appraisal of the rate pressure product as index of myocardial oxygen consumption for the study of metabolic coronary flow regulation.

For the assessment of metabolic coronary vasodilatation, changes in systolic rate pressure product (RPP) are frequently used to estimate the pacing- or exercise induced changes in myocardial oxygen consumption (MVO2). The present study was designed to test whether this is justified in patients with coronary artery disease. To study the relation between RPP and changes in MVO2 under different conditions, we used data from 21 patients who participated in two previous studies investigating the effect of nitroglycerin (NTG) and anaesthesia on metabolic coronary flow regulation. At control, during administration of NTG 1 microg/kg/min (n=11), and during anaesthesia (n=10), coronary sinus blood flow, MVO2 and RPP were measured at sinus rhythm and during atrial pacing (30 bpm above sinus rate) and the relation between the percentage increase in RPP (delta%RPP) and MVO2 delta%MVO2) was analysed, using standard linear regression analysis. Although a significant relation between delta%MVO2 and delta%RPP was found at control and during anaesthesia, prediction intervals were very wide and only 40% and 60% of the variation in delta%MVO2, respectively, could be explained by the variation in delta%RPP. During administration of NTG 1 microg/kg/min no significant relation was found between delta%MVO2 and delta%RPP. Thus, for the study of metabolic coronary flow regulation, pacing induced changes in MVO2 cannot be predicted accurately from changes in RPP.

The effect of nitroglycerin on pacing-induced changes in myocardial oxygen consumption and metabolic coronary vasodilation in patients with coronary artery disease.

UNLABELLED: In the present study, we assessed the potential effect of nitroglycerin IV (NTG), a donor of exogenous nitric oxide, on metabolic coronary flow control in patients with coronary artery disease. In 12 patients scheduled for coronary artery surgery, arterial blood pressure, pulmonary capillary wedge pressure, coronary sinus blood flow (continuous thermodilution), myocardial oxygen supply (DVO2), and myocardial oxygen consumption (MVO2) were measured at sinus rhythm and in response to atrial pacing at 30 bpm greater than baseline sinus rate. These measurements were repeated during infusion of NTG 1 and 2 microg x kg(-1) x min(-1). At control, in the absence of NTG, MVO2 increased from 13.7 +/- 3.4 mL O2/min during sinus rhythm to 19.3 +/- 5.5 mL O2/min during pacing. NTG 1 and 2 microg x kg(-1) x min(-1) blunted the pacing-induced increase in MVO2 dose-dependently. During NTG 1 microg x kg(-1) x min(-1), MVO2 increased from 12.9 +/- 3.3 mL O2/min at sinus rhythm to 17.3 +/- 4.7 mL O2/min during pacing (P = 0.01 versus control pacing); during NTG 2 microg x kg(-1) x min(-1), MVO2 increased from 13.4 +/- 3.3 mL O2/min to 15.9 +/- 3.7 mL O2/min (P = 0.008 versus control pacing). However, the pacing-induced increase in DVO2 per mL O2/min increase in MVO2 (delta DVO2/delta MVO2), was significantly greater during the infusion of NTG 2 microg x kg(-1) x min(-1) (1.85 +/- 0.56; P = 0.023) compared with control (1.51 +/- 0.22). This was associated with an increase in coronary sinus hemoglobin oxygen saturation (30% +/- 5% at control pacing and 34% +/- 6% during pacing with NTG 2 microg x kg(-1) x min(-1); P = 0.018), which indicates that during the infusion of NTG, there was more metabolic coronary vasodilation than achievable solely on the basis of the metabolic stimulus. IMPLICATIONS: Our findings suggest that nitroglycerin, a donor of exogenous nitric oxide, reduces pacing-induced increases in myocardial oxygen consumption and enhances metabolic coronary vasodilation in patients with coronary artery disease, in whom endogenous nitric oxide activity may be reduced.

Intracoronary-administered urapidil does not influence myocardial contractility, metabolic activity, or coronary sinus blood flow in humans.

OBJECTIVE: To compare the acute effect of intracoronary administration of urapidil and saline on myocardial contractility and metabolic activity. DESIGN: Prospective, controlled, open-label study. SETTING: University teaching hospital. PARTICIPANTS AND INTERVENTIONS: Eight patients with stable coronary artery disease (CAD) undergoing elective percutaneous transluminal coronary angioplasty (PTCA) received normal saline followed by urapidil, 4 mg, injected directly into the left main coronary artery. MEASUREMENTS AND MAIN RESULTS: Because local intracoronary administration is a non-steady-state condition, an in vitro model was used before the clinical experiments to establish the kinetic effects of acute administration of urapidil. The clinical experiments were performed in eight patients with CAD after PTCA. Measurements included a complete hemodynamic profile, coronary sinus blood flow (continuous thermodilution), left ventricular (LV) peak (+) dP/dt, LV peak (-) dP/dt, LV dP/dt/P(D)40, and LV end-diastolic pressures. Arterial and coronary venous blood samples were also obtained for the calculation of myocardial oxygen consumption. Baseline measurements I were first obtained, followed by intracoronary injection of 2 mL of saline. Additional measurements were obtained 1, 5, and 10 minutes after administration of saline. After a resting period (15 minutes), baseline measurements II, and intracoronary injection of urapidil, 4 mg (dissolved in 2 mL saline), additional measurements were obtained 1, 5, and 10 minutes later. Heart rate decreased 2.7+/-3.5 beats/min after injection of saline, whereas heart rate increased 2.0+/-1.8 beats/min after intracoronary urapidil, resulting in a significant difference in treatment effect (p = 0.003). There were no additional differences in treatment effect for any of the other measured or calculated parameters reflecting systemic hemodynamics, LV contractility, coronary dynamics, and myocardial metabolic activity. CONCLUSION: The results suggest that intracoronary bolus administration of preservative-free urapidil, 4 mg, is not associated with any detectable effect on myocardial contractility or coronary smooth muscle in awake nonsurgical patients with CAD, after PTCA.

A randomized multicenter double-blind comparison of urapidil and ketanserin in hypertensive patients after coronary artery surgery.

OBJECTIVES: To compare the hemodynamic responses, safety, and efficacy of urapidil and ketanserin in hypertensive patients after coronary artery surgery. DESIGN: Randomized double-blind study. SETTING: Multi-institutional. PARTICIPANTS: One hundred twenty-two patients undergoing elective coronary artery surgery. INTERVENTIONS: When hypertension (defined as mean arterial pressure > 85 mmHg) developed within the first 2 hours after arrival in the intensive care unit, patients received urapidil (n = 62) or ketanserin (n = 60) to reach a mean arterial pressure between 65 and 75 mmHg. Urapidil was administered by repeated bolus injections (25 to 125 mg) followed by a continuous infusion of maximally 50 micrograms/kg/min. Ketanserin was administered by repeated bolus injections (10 to 50 mg) followed by a continuous infusion of maximally 4.0 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: A complete hemodynamic profile was determined at baseline and at 30 and 60 minutes after start of study medication. In the urapidil group, mean arterial pressure (+/-SD) decreased significantly from 100.6 +/- 12.4 mmHg at baseline to 74.6 +/- 12.1 mmHg at 30 minutes and 73.5 +/- 13.8 mmHg at 60 minutes. In the ketanserin group, mean arterial pressure decreased significantly from 98.7 +/- 10.7 mmHg at baseline to 83.5 +/- 16.8 mmHg at 30 minutes and 83.1 +/- 15.3 mmHg at 60 minutes. Between the groups, there was a significant difference in the degree of lowering mean arterial pressure at 30 and 60 minutes. Heart rate increased significantly by 5.8 +/- 12.7 (30 minutes) and 8.6 +/- 16.5 (60 minutes) beats/min in the ketanserin group. In the urapidil group, no changes in heart rate occurred. Cardiac output increased to the same extent (0.7 L/min) in both groups. Within and between the groups, there were no relevant changes in pulmonary filling pressures. The number of patients not responding adequately to the study medication (mean arterial pressure > 85 mmHg after 30 minutes despite the maximum doses of study medication) was comparable in both groups (9 [U] v 13 [K]). Adverse events attributable to the study medication occurred to a similar degree in both groups. In the patients treated with urapidil, a significantly higher incidence (32.3%) of hypotension (mean arterial pressure < or = 65 mmHg for more than 10 minutes) occurred after 60 minutes of continuous infusion. CONCLUSIONS: In contrast to ketanserin, urapidil did not increase heart rate. Urapidil was more effective in lowering arterial blood pressure than ketanserin. However, one third of the patients treated with urapidil developed hypotension after 60 minutes of continuous infusion.

Myocardial oxygen supply:demand ratio as reference for coronary vasodilatory drug effects in humans.

OBJECTIVE: Introduction and measurement of human myocardial oxygen supply:demand ratio as a reference for quantification of coronary microvascular vasodilating drug effects in clinical studies. Myocardial oxygen consumption is the major determinant of coronary blood flow; therefore, the true vasodilating properties of coronary vasodilating drugs that may have an effect on oxygen consumption cannot be correctly assessed from blood flow changes alone. DESIGN: Prospective, controlled trial. SETTING: Academic hospital. PATIENTS: 12 patients with multivessel coronary artery disease (CAD) undergoing coronary artery bypass grafting. INTERVENTIONS: Cardiac pacing at 30 beats/min above sinus rhythm in awake and anaesthetised patients (fentanyl/pancuronium bromide). MAIN OUTCOME MEASURES: Myocardial oxygen supply, defined as coronary sinus blood flow multiplied by arterial oxygen content; myocardial oxygen demand, defined as coronary sinus blood flow multiplied by arteriovenous oxygen content difference. The change in oxygen demand induced by pacing was related to the change in myocardial oxygen supply in awake and anaesthetised patients. This myocardial oxygen supply:demand ratio determined in the reference study was compared with that induced by intravenous and intracoronary drugs (nifedipine, felodipine, urapidil, and sodium nitroprusside) in two pharmacological studies: patients with CAD undergoing cardiac surgery (45 treated with sodium nitroprusside, 27 with nifedipine, and 27 with urapidil to manage arterial blood pressure); and patients with unstable angina (and a similar degree of CAD) undergoing cardiac catheterisation for diagnostic purposes (10 treated with intracoronary nifedipine and 10 with intracoronary felodipine). RESULTS: When awake, the ratio of pacing induced oxygen supply:demand changes in the 12 reference study patients was 1.50 (95% confidence intervals (CI), 1.41-1.58), similar to the 1.45 (1.35-1.56) measured in the same patients after induction of anaesthesia. Anaesthesia per se did not increase coronary oxygen supply above the expected increase related to demand changes. The only significant change in the oxygen supply:demand ratio was induced by intracoronary bolus administration of nifedipine and felodipine (10.6 (SE 1.9) and 13.9 (1.9) ml/min, respectively, above the demand related supply). CONCLUSIONS: Quantification of coronary vasoactive properties in relation to the physiological reference ratio between myocardial oxygen supply and demand may be a powerful tool to differentiate between true and apparent coronary vasoactive drugs.

Rate of coronary flow adaptation in response to changes in heart rate before and during anesthesia for coronary artery surgery.

BACKGROUND: The rate of adaptation of coronary blood flow in response to stepwise changes in heart rate (HR) has been extensively studied in dogs and goats to improve our understanding of the dynamics of coronary regulation processes and their pathophysiology and to obtain time constants for mathematical modeling of the coronary regulation. However, little is known about the dynamic characteristics of coronary flow adaptation in humans. In patients undergoing coronary artery surgery, we investigated the rate of coronary adaptation in response to stepwise changes in HR, in the awake and anesthetized states. METHODS: In 11 patients with stable coronary artery disease, arterial blood pressure, right atrial pressure, and coronary sinus blood flow, measured by continuous thermodilution, were calculated per beat. The ratio of beat-averaged arterial blood pressure minus right atrial pressure and coronary sinus blood flow was calculated to obtain an index of coronary resistance. The rate of change of coronary resistance index was quantified by t50, defined as the time required to establish 50% of the total change in coronary resistance index. Responses of coronary resistance index after HR changes, before and after induction of anesthesia, were compared. The anesthesia technique consisted of 100 micrograms.kg-1 fentanyl and 0.1 mg.kg-1 pancuronium bromide in combination with oxygen in air ventilation (FIO2 = 0.5). RESULTS: In the awake situation, t50 values of the dilating and constricting responses, induced by an increase and a decrease in HR were 5.0 +/- 2.1 (SD) s (range 2.6-9.0 s) and 5.7 +/- 1.2 s (range 4.1-7.8 s), respectively. During fentanyl/pancuronium anesthesia, the rate of coronary flow adaptation was significantly slower, with t50 values of 10.2 +/- 2.1 s (range 7.7-13.1 s) after an HR step-up and 9.8 +/- 2.1 s (range 6.6-13.2 s) after an HR step-down. Compared to the awake situation, arterial blood pressure was significantly reduced during anesthesia, but coronary vascular resistance remained unchanged. This implies that the steady-state static regulation of coronary blood flow had not changed. CONCLUSIONS: These preliminary data suggest that, in patients with coronary artery disease, the rate of change in coronary vascular resistance in response to pacing-induced changes in HR is mitigated by fentanyl/pancuronium anesthesia during positive pressure ventilation. A further qualification of our findings in a larger number of patients is warranted.

Comparison of the effects of urapidil and sodium nitroprusside on haemodynamic state, myocardial metabolism and function in patients during coronary artery surgery.

We have compared, in an open randomized study, the effects of sodium nitroprusside (SNP) and urapidil on haemodynamic state and myocardial function and metabolism in two groups of patients undergoing elective coronary artery surgery. Sixty patients were allocated randomly to one of two groups: group SNP (n = 29) received SNP at an initial rate of 1-2 micrograms kg-1 min-1; group URA (n = 31) received one or more bolus injections of urapidil 25 mg and an i.v. infusion at an initial rate of 11-21 micrograms kg-1 min-1. Baseline measurements were obtained 10 min after introduction of an echotransducer into the oesophagus. Subsequently, vasodilator therapy was started in both groups. Infusion rates were adjusted to maintain systolic arterial pressure at 80-120% of baseline values (or mean arterial pressure < 100 mm Hg). Additional measurements were obtained 10 min after the start of vasodilator therapy and after sternotomy when the pericardium was opened. At each measuring time a complete haemodynamic profile, coronary sinus blood flow (CSBF) curves, transoesophageal echocardiographic images, and arterial and coronary venous blood samples were obtained. Arterial pressure was controlled adequately in both groups. After sternotomy, heart rate and cardiac index increased in both groups. At that time, there was a significant increase in myocardial oxygen consumption and CSBF in group URA (P < 0.05). However, the ratio between myocardial oxygen demand and oxygen supply remained unchanged and there was no difference in the number of ischaemic episodes between the groups.