Peripherally applied opioids for postoperative pain: evidence of an analgesic effect? A systematic review and meta-analysis.

BACKGROUND: Opioids applied peripherally at the site of surgery may produce postoperative analgesia with few side effects. We performed this systematic review to evaluate the analgesic effect of peripherally applied opioids for acute postoperative pain. METHODS: We searched PubMed (1966 to June 2013), Embase (1980 to June 2013), and the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 6). Randomized controlled trials investigating the postoperative analgesic effect of peripherally applied opioids vs. systemic opioids or placebo, measured by pain intensity scores, consumption of supplemental analgesics and time to first analgesic were included. Trials with sample sizes of fewer than 10 patients per treatment group or trials with opioids administered intra-articularly or as peripheral nerve blocks were excluded. RESULTS: Data from 26 studies, including 1531 patients and 13 different surgical interventions were included. Clinical heterogeneity of the studies was substantial. Meta-analysis indicated statistically significant, but not clinically relevant, reductions in VAS score at 6-8 h (mean difference -4 mm, 95% CI: -6 to -2) and 12 h postoperatively (mean difference -5 mm, 95% CI: -7 to -3) for peripherally applied opioids vs. placebo and statistically significant increased time to first analgesic (mean difference 153 min, 95% CI: 41-265). When preoperative inflammation was reported (five studies), peripherally applied opioids significantly improved postoperative analgesia. CONCLUSION: Evidence of a clinically relevant analgesic effect of peripherally applied opioids for acute postoperative pain is lacking. The analgesic effect of peripherally applied opioids may depend on the presence of preoperative inflammation.

Intraoperative transfusion threshold and tissue oxygenation: a randomised trial.

BACKGROUND AND OBJECTIVES: Transfusion with allogeneic red blood cells (RBCs) may be needed to maintain oxygen delivery during major surgery, but the appropriate haemoglobin (Hb) concentration threshold has not been well established. We hypothesised that a higher level of Hb would be associated with improved subcutaneous oxygen tension during major spinal surgery. MATERIALS AND METHODS: Fifty patients aged 18 years or older scheduled for spinal fusion with instrumentation were included and randomised to receive RBCs at either a Hb concentration of 7·3 g dL(-1) (restrictive group) or a Hb concentration of 8·9 g dL(-1) (liberal group) (Registration no.: H-C-2009-072). Oxygen tension was measured with a polarographic electrode placed subcutaneously over the left deltoid muscle. The primary endpoint was subcutaneous oxygen tension at the time most patients were still undergoing surgery. RESULTS: Forty-eight patients were included in the intention-to-treat analysis; 25 patients in the restrictive group and 23 patients in the liberal group. The median change in subcutaneous oxygen tension 60 min after surgical incision was -0·79 and -0·75 kPa in the restrictive and the liberal groups, respectively (P = 0·78). No significant difference was found in the lowest subcutaneous oxygen tension; -2·07 vs. -1·95 kPa in the restrictive and the liberal groups, respectively (P = 0·85). CONCLUSION: A Hb concentration transfusion threshold of 8·9 g dL(-1) was not associated with a higher subcutaneous oxygen tension during major spinal surgery than a threshold of 7·3 g dL(-1), but the trial was compromised by methodological difficulties.

Stuck long-term indwelling central venous catheters in adolescents: three cases and a short topical review.

We present three cases of fixated vascular injection ports. Two patients had cystic fibrosis and one had an immunological defect. All catheters were made from polyurethane and implanted in adolescent patients. Indwelling time were 6-8 years. One patient's catheter was entirely integrated in the vessel wall and impossible to remove. In the other two cases, catheters were removed with great difficulty by the interventional radiologists. These cases raise important questions concerning the maximum indwelling time and the choice of catheter material when implanting permanent central venous catheters (CVCs) in adolescents. Furthermore, it highlights the importance of not breaking a CVC in the attempt to remove it.

Depth of anaesthesia monitoring in obese patients: a randomized study of propofol-remifentanil.

BACKGROUND: In obese patients, depth of anaesthesia monitoring could be useful in titrating intravenous anaesthetics. We hypothesized that depth of anaesthesia monitoring would reduce recovery time and use of anaesthetics in obese patients receiving propofol and remifentanil. METHODS: We investigated 38 patients with a body mass index >or=30 kg/m(2) scheduled for an abdominal hysterectomy. Patients were randomized to either titration of propofol and remifentanil according to a cerebral state monitor (CSM group) or according to usual clinical criteria (control group). The primary end point was time to eye opening and this was assessed by a blinded observer. RESULTS: Time to eye opening was 11.8 min in the CSM group vs. 13.4 min in the control group (P=0.58). The average infusion rate for propofol was a median of 516 vs. 617 mg/h (P=0.24) and for remifentanil 2393 vs. 2708 microg/h (P=0.04). During surgery, when the cerebral state index was continuously between 40 and 60, the corresponding optimal propofol infusion rate was 10 mg/kg/h based on ideal body weight. CONCLUSION: No significant reduction in time to eye opening could be demonstrated when a CSM was used to titrate propofol and remifentanil in obese patients undergoing a hysterectomy. A significant reduction in remifentanil consumption was found.

Pre-operative fasting guidelines: an update

Liberal pre-operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children <6 months, most recommendations now allow breast- or formula milk feeding up to 4 h before anaesthesia.Recently, the concept of pre-operative oral nutrition using a special carbohydrate-rich beverage has also gained support and been shown not to increase gastric fluid volume or acidity. Based on the available literature, our Task Force has produced new consensus-based Scandinavian guidelines for pre-operative fasting. What is still not clear is to what extent the new liberal fasting routines should apply to patients with functional dyspepsia or systematic diseases such as diabetes mellitus. Other still controversial areas include the need for and effect of fasting in emergency patients, women in labour and in association with procedures done under ‘deep sedation’. We think more research on the effect of various fasting regimes in subpopulations of patients is needed before we can move one step further towards completely evidence-based pre-operative fasting guidelines.

Pre-operative fasting guidelines: an update.

Liberal pre-operative fasting routines have been implemented in most countries. In general, clear fluids are allowed up to 2 h before anaesthesia, and light meals up to 6 h. The same recommendations apply for children and pregnant women not in labour. In children <6 months, most recommendations now allow breast- or formula milk feeding up to 4 h before anaesthesia. Recently, the concept of pre-operative oral nutrition using a special carbohydrate-rich beverage has also gained support and been shown not to increase gastric fluid volume or acidity. Based on the available literature, our Task Force has produced new consensus-based Scandinavian guidelines for pre-operative fasting. What is still not clear is to what extent the new liberal fasting routines should apply to patients with functional dyspepsia or systematic diseases such as diabetes mellitus. Other still controversial areas include the need for and effect of fasting in emergency patients, women in labour and in association with procedures done under 'deep sedation'. We think more research on the effect of various fasting regimes in subpopulations of patients is needed before we can move one step further towards completely evidence-based pre-operative fasting guidelines.

Peroperative depth of anaesthesia may influence postoperative opioid requirements.

BACKGROUND: Studies on monitoring the depth of anaesthesia have shown that with the use of these monitors the peroperative consumption of anaesthetics can be reduced. Studies have also indicated that the peroperative depth of anaesthesia may affect the postoperative course. The purpose of this study was to evaluate a possible relation between the depths of anaesthesia and the postoperative pain score and consumption of morphine. METHODS: We used middle latency auditory evoked potentials (MLAEPs) for monitoring the depth of anaesthesia. The study was prospective, observer blinded and included 50 women scheduled for elective abdominal hysterectomy. Anaesthesia was induced using propofol and remifentanil. Before leaving the recovery room the patients were provided with a programmed patient-controlled pump (PCA), which was only activated on demand. Auditory evoked potentials were registered from just before induction of anaesthesia and during the whole procedure, but the anaesthetist did not have access to the monitor. RESULTS: Fifty patients were included and seven were excluded. The remaining 43 patients were divided into two groups: Group High (n=12) with an AAI>28 for >5% of the registration time and Group Low (n=31) with an AAI>28 for <5% of the registration time. Group High had significantly higher morphine requirements in the recovery and activated the PCA-pump more frequently during the first 24 postoperative hours. CONCLUSION: The results indicate that the peroperative depth of anaesthesia may have effects on the postoperative analgesic requirements.

Caudal bupivacaine supplemented with caudal or intravenous clonidine in children undergoing hypospadias repair: a double-blind study.

BACKGROUND: Clonidine is used increasingly in paediatric anaesthetic practice to prolong the duration of action of caudal block with a local anaesthetic agent. Which route of administration of clonidine is the most beneficial remains unknown. We compared the effects of caudal and i.v. clonidine on postoperative analgesia produced by caudal bupivacaine after hypospadias repair. METHODS: Forty-six children (ASA I or II) aged 24-104 months received standardized premedication with midazolam, a general anaesthetic and a caudal block with bupivacaine 0.25%, 0.5 ml kg(-1). The children were randomized in a double-blind fashion to two groups: the i.v. group received clonidine 2 micro g kg(-1) i.v. and simultaneously the same volume of saline caudally. The caudal group received clonidine 2 micro g kg(-1) caudally and a similar volume of saline i.v. After surgery, all children received acetaminophen 20 mg kg(-1) rectally or orally 6-hourly and were given a patient-controlled or nurse-controlled analgesia (PCA/NCA) pump with i.v. morphine (bolus of 25 micro g kg(-1) and an 8-min lockout period with no background infusion). Monitoring of scores for pain, sedation, motor block, and postoperative nausea and vomiting was performed by nurses blinded to the study allocations. Time to first activation of the PCA/NCA pump and 0-24 h and 24-48 h morphine consumption were also recorded. RESULTS: Forty-four children completed the study. Age, weight and duration of anaesthesia and surgery were similar in the two groups. The median (range) time to first activation of the PCA/NCA pump was similar in the two groups: 425 (150-1440) min in the i.v. group and 450 (130-1440) min in the caudal group. The number of children not requiring postoperative morphine was four and seven respectively. Morphine consumption during 0-24 h and 24-48 h was similar between groups. CONCLUSIONS: The analgesic effect of clonidine 2 micro g kg(-1) as an adjunct to caudal block with bupivacaine 0.25%, 0.5 ml kg(-1) is similar whether administered i.v. or caudally.

Comparison of auditory evoked potentials and the A-line ARX Index for monitoring the hypnotic level during sevoflurane and propofol induction.

BACKGROUND: Extraction of the middle latency auditory evoked potentials (AEP) by an auto regressive model with exogenous input (ARX) enables extraction of the AEP within 1.7 s. In this way, the depth of hypnosis can be monitored at almost real-time. However, the identification and the interpretation of the appropriate signals of the AEP could be difficult to perform during the anesthesia procedure. This problem was addressed by defining an index which reflected the peak amplitudes and latencies of the AEP, developed to improve the clinical interpretation of the AEP. This index was defined as the A-line Arx Index (AAI). METHODS: The AEP and AAI were compared with the Modified Observers Assessment of Alertness and Sedation Scale (MOAAS) in 24 patients scheduled for cardiac surgery, anesthetized with propofol or sevoflurane. RESULTS: When comparing the AEP peak latencies and amplitudes and the AAI, measured at MOAAS level 5 and level 1, significant differences were achieved. (mean(SD) Nb latency: MOAAS 5 51.1 (7.3) ms vs. MOAAS 1: 68.6 (8.1) ms; AAI: MOAAS 5 74.9 (13.3) vs. MOAAS 1 20.7 (4.7)). Among the recorded parameters, the AAI was the best predictor of the awake/anesthetized states. CONCLUSION: We conclude that both the AAI values and the AEP peak latencies and amplitudes correlated well with the MOAAS levels 5 (awake) and 1 (anesthetized).

Changes in circulating blood volume after infusion of hydroxyethyl starch 6% in critically ill patients.

BACKGROUND: The cardiovascular response to a volume challenge with hydroxyethyl starch (HES) (200/0.5) 6% depends on the relation between the volume of HES 6% infused and the expansion of the blood volume in critically ill patients. However, only relatively limited data exist on the plasma expanding effect of infusion of HES 6% in critically ill patients. The purpose of the study was to evaluate the variation in the expansion of the circulating blood volume (CBV) in critically ill patients after infusion of 500 ml of colloid (HES (200/0.5) 6%) using the carbon monoxide method. METHODS: In 20 consecutive patients admitted to the ICU requiring mechanical ventilation and volume expansion, 500 ml of HES (200/0.5) 6% was infused. The CBV was measured immediately before the infusion, 10 min after completing the infusion and then hourly for 8 h. RESULTS: The median volume expansion immediately after infusion was 470 ml (range 270 ml to 840 ml). The corresponding values after 4 h and 8 h were 265 ml (range -30 ml to 460 ml) and 120 ml (range -210 ml to 360 ml), respectively. The increase in CBV was only statistically significant for 4 h. The coefficient of variation of the method for estimation of CBV was 3.6%. CONCLUSIONS: The large interindividual variation of the volume expansion after infusion of HES 6% in critically ill patients illustrates one of the difficulties in optimizing colloid therapy and interpretating the changes in hemodynamic variables after a colloid challenge.

Pharmacokinetics of rectal paracetamol after repeated dosing in children.

Twenty-three children (aged between 9 weeks and 11 yr) were given paracetamol suppositories 25 mg kg-1 every 6 h (maximum 5 days) after major surgery and serum and saliva concentrations were measured. There was a good correlation (r = 0.91, P < 0.05) between saliva and serum concentrations. A one-compartment linear model with first-order elimination and absorption and lag-time was fitted to the data (ADAPT II). At steady state, the mean (SD) concentration was 15.2 (6.8) mg litre-1. Mean (SD) time to reach 90% of the steady state concentration was 11.4 (8.6) h. Body weight, age and body surface area were well correlated (P < 0.05) with clearance and apparent volume of distribution. There was no evidence of accumulation leading to supratherapeutic concentrations during this dosing schedule for a mean of approximately 2-3 days.

Thermodilution versus inert gas rebreathing for estimation of effective pulmonary blood flow.

OBJECTIVE: To compare measurements of the effective pulmonary blood flow (Qep, i.e., nonshunted fraction of cardiac output, Qt) by the inert gas rebreathing (RB) method and the thermodilution (TD) technique in critically ill patients. DESIGN: Prospective, comparative study of a noninvasive method and an established invasive technique. SETTING: An 11-bed general intensive care unit in a university hospital. PATIENTS: A total of 14 critically ill patients, all mechanically ventilated and monitored with systemic and pulmonary artery catheters. MEASUREMENTS AND MAIN RESULTS: Qep was determined in duplicate by RB using a mass spectrometer for gas analysis. For each determination, Qt was measured in triplicate by the cold water bolus TD technique and averaged. Simultaneously mixed venous and arterial blood samples were analyzed to calculate the intrapulmonary shunt fraction and thereby convert estimates of Qt to Qep. Mean difference between paired estimates (RB - TD) was 0.01 L/min, so for differences was 1.19 L/min, and 95% confidence interval for the bias was -0.45 to 0.47 L/min. Coefficients of variation for repeated Qep estimates were 8% (RB) and 12% (TD), respectively. Coefficients of variation for RB estimates of functional residual capacity and lung tissue volume were 6% and 17%, respectively. CONCLUSIONS: The RB method is a promising method for simultaneous noninvasive estimation of Qep and functional residual capacity in mechanically ventilated patients. However, further investigations are needed to evaluate potential problems of the method before it can be recommended for clinical purposes.

[Nitrogen oxide inhalation in critically ill patients]. / Inhaleret nitrogenoxid til kritisk syge patienter.

Inhaled nitric oxide (iNO) has been extensively used in the treatment of severe hypoxaemic respiratory failure and/or pulmonary hypertension. Although the majority of studies have almost consistently demonstrated a beneficial effect on oxygenation and a reduction in pulmonary artery pressures, none of the randomised trials have reported a reduced mortality using iNO on patients with severe respiratory failure. In neonates with severe respiratory failure and pulmonary hypertension, however, iNO can reduce the need of extracorporal membrane oxygenation. Prior to using iNO on adult patients we suggest other measures to be taken (i.e. optimising ventilator settings, ventilation in prone position).

Tetracaine gel vs EMLA cream for percutaneous anaesthesia in children.

We have evaluated the anaesthetic effect of tetracaine gel 1 g, applied for 45 min, compared with EMLA cream 2 g, applied for 60 min, in a randomized, double-blind study in 60 children aged 3-15 yr. Venous cannulation was performed 15 min after removal of the EMLA cream (n = 20) and tetracaine gel (n = 20). Cannulation was performed up to 215 min after removal of the tetracaine gel in another 20 patients. Significantly lower pain scores were recorded by the children treated with tetracaine gel compared with EMLA cream (P < 0.02). Forty to 45% of children in the tetracaine groups reported no pain compared with only 10% in the EMLA group. Only minor adverse effects were observed. We conclude that tetracaine gel provided effective, rapid, long-lasting and safe local anaesthesia, and was significantly better than EMLA cream in reducing pain during venous cannulation in children using the recommended application periods for both formulations.

Identification of causal relations between haemodynamic variables, auditory evoked potentials and isoflurane by means of fuzzy logic.

The aim of this study was to identify a possible relationship between haemodynamic variables, auditory evoked potentials (AEP) and inspired fraction of isoflurane (ISOFl). Two different models (isoflurane and mean arterial pressure) were identified using the fuzzy inductive reasoning (FIR) methodology. A fuzzy model is able to identify non-linear and linear components of a causal relationship by means of optimization of information content of available data. Nine young female patients undergoing hysterectomy under general anaesthesia were included. Mean arterial pressure (MAP), heart rate (HR), end-tidal expired carbon dioxide (CO2ET), AEP and ISOFl were monitored with a sampling time of 10 s. The AEP was extracted using an autoregressive model with exogenous input (ARX model) which decreased the processing time compared with a moving time average. The AEP was mapped into a scalar, termed the depth of anaesthesia index (DAI) normalized to 100 when the patient was awake and descending to an average of 25 during loss of consciousness. The FIR methodology identified those variables among the input variables (MAP, HR, CO2ET, DAI or ISOFl) that had the highest causal relation with the output variables (ISOFl and MAP). The variables with highest causal relation constitute the ISOFl and MAP models. The isoflurane model predicted the given anaesthetic dose with a mean error of 12.1 (SD 10.0)% and the mean arterial pressure model predicted MAP with a mean error of 8.5 (7.8)%.