Capnodynamic determination of cardiac output in hypoxia-induced pulmonary hypertension in pigs.

BACKGROUND: Effective pulmonary blood flow (COEPBF) has recently been validated for its ability to measure cardiac output (CO) in children and animals. This study compared COEPBF with the Fick method (COFick) and CO measurements using an invasive pulmonary artery flow probe (COTS). The aim of the study was to validate COEPBF against these reference methods in a porcine model of hypoxia-induced selective pulmonary hypertension. METHODS: Ten anaesthetised mechanically ventilated piglets (median weight 23.9 kg) were exposed to a hypoxic gas mixture inducing selective pulmonary hypertension. Pulmonary hypertension was subsequently reversed with inhaled nitric oxide. Simultaneous recordings of COEPBF, COFick, and COTS were performed throughout the protocol and examined for agreement and trending ability. RESULTS: Overall bias (Bland-Altman) between COEPBF and COTS was 0.2 L min-1 (limits of agreement -0.5 and +0.9 L min-1) with a mean percentage error of 25%. Overall bias between COEPBF and COFick was -0.1 L min-1 (limits of agreement -0.9 and +0.6 L min-1) and a mean percentage error of 25%. The concordance rate was 86% for COEPBF when compared with COTS using a 10% exclusion zone. CONCLUSIONS: Estimation of CO with COEPBF results in values very close to the gold standard reference methods COFick and COTS. COEPBF appears to be an accurate tool for monitoring absolute values and changes in CO during hypoxia-induced pulmonary hypertension and inhaled nitric oxide treatment.

Plasma concentrations of alpha-1-acid glycoprotein in preterm and term newborns: influence of mode of delivery and implications for plasma protein binding of local anaesthetics.

BACKGROUND: Alpha-1-acid glycoprotein (AAGP) is an acute-phase protein with high affinity for amide local anaesthetics (LAs), and a major determinant of free and potentially toxic concentrations of LAs in plasma. Neonates are known to have lower plasma concentrations of AAGP than adults, and are at risk of developing high free concentrations of LAs. Data regarding AAGP in newborns are so far sparse. The aim of this study was to determine plasma concentrations of AAGP after delivery of preterm and term infants, and to investigate correlations between AAGP and gestational age, birth weight, gender, and mode of delivery. METHODS: In this prospective observational study, blood was sampled from umbilical cords of 70 newborn infants born at gestational weeks 27-42 immediately after delivery. Blood samples were subsequently analysed for AAGP plasma concentrations with an immunoturbidimetric assay. RESULTS: We found higher concentrations of AAGP in infants born vaginally compared with those who were delivered by elective Caesarean section [median (inter-quartile range) 0.189 g litre-1 (0.142-0.263 g litre-1) vs 0.110 g litre-1 (0.094-0.157 g litre-1; P=0.0003)], respectively. There was a correlation between gestational age and AAGP concentrations (r=0.50; P=0.011), with significantly higher concentrations in the more mature infants. Gender and birth weight did not appear to influence the plasma concentrations of AAGP. CONCLUSIONS: Alpha-1-acid glycoprotein concentrations in newborns are influenced both by gestational age and mode of delivery. Thus, when dosing local anaesthetics in a parturient, these factors should be taken into account.

Validation of capnodynamic determination of cardiac output by measuring effective pulmonary blood flow: a study in anaesthetised children and piglets.

BACKGROUND: Effective pulmonary blood flow (COEPBF) has recently been validated as a technique for determining cardiac output (CO) in animals of varying sizes. The primary aim of our study was to investigate this new technique in paediatric surgical patients, compared with suprasternal two-dimensional Doppler (COSSD). METHODS: A total of 15 children undergoing cleft lip/palate surgery were investigated. Before the start of surgery, manoeuvres that were anticipated to reduce (increase in PEEP from 3 to 10 cm H2O) and increase (atropine) CO were undertaken. A study in mechanically ventilated piglets was also undertaken under general anaesthesia, measuring COEPBF and pulmonary artery (COTS) flow by ultrasonic probe as the comparator. Bias (Bland-Altman plots) and limits of agreement were assessed for effective pulmonary blood flow and COSSD or COTS. RESULTS: In paediatric patients (median age 8.5 months), overall bias was -8.1 (limits of agreement -82 to +66) ml kg-1 min-1, with a mean percentage error of 48% and a concordance rate of 64%. In the piglet model, overall bias was -1 (-36 to +38) ml kg-1 min-1, with a mean percentage error of 31% and a concordance rate of 95%. CONCLUSIONS: Under controlled experimental conditions, COEPBF is associated with excellent agreement and good trending ability when compared with the gold standard COTS. In the paediatric clinical setting, COEPBF performs well; by contrast, COSSD, an operator- and anatomy-dependent technology, appears less reliable than COEPBF.

Volumes of the spinal canal and caudal space in children zero to three years of age assessed by magnetic resonance imaging: implications for volume dosage of caudal blockade.

BACKGROUND: The primary aim of this study was to objectively assess the different spinal and caudal volumes that are of interest for caudal block volume dosing. METHODS: Three directly assessed (volume of spinal canal/caudal space, volume of the dural sac and volume of spinal cord) and two derived volumes (volume of the epidural space and cerebrospinal fluid volume) were determined from magnetic resonance images (MRI) in 20 children (zero - three yr of age). The assessed volumes were correlated to age, height and weight. Furthermore, the volumes of the epidural space from caudal canal to three different clinically relevant target levels (L 1, Th 10 and Th 6) and the epidural volume of each individual spinal segment at the caudal, lumbar and thoracic levels were calculated. RESULTS: All volumes correlated in a linear manner to length and weight (R2 0.614 - 0.867) whereas a curvilinear correlation was associated with best curve fit for age (R2 0.696 - 0.883). The median volumes of the epidural space from caudal canal to L 1, Th 10 and Th 6 were 1.30 ml kg-1 (95%CI 1.08-1.51), 1.57 ml kg-1 (95%CI 1.29-1.81) and 1.78 ml kg-1 (95%CI 1.52-2.08), respectively. The median volumes of the epidural space per vertebral segment were Thoracic: 0.60 ml (95%CI 0.38-0.75); Lumbar: 1.18 ml (95%CI 0.94-1.43) and Caudal: 0.85 ml (95%CI 0.56-1.18). CONCLUSIONS: The spinal volumes of interest show a linear correlation to height and weight whereas a curvilinear correlation was found for age. The volume of the epidural space per segment was found to be significantly higher at the lumbar level compared with the caudal and thoracic levels.

Etomidate exposure in early infant mice (P10) does not induce apoptosis or affect behaviour.

BACKGROUND: Numerous animal studies have shown that all commonly used intravenous anaesthetic drugs and volatile agents may cause neuronal apoptosis following exposure in early life. Most studies have focussed on detecting increased apoptosis but their methods are not always readily transferrable to humans. The lipid formulation of etomidate represents an alternative to the currently established intravenous anaesthetic agents but there is no animal or human data on apoptosis or long-term behavioural changes. The aim of our study was to investigate the effects of etomidate on cerebral neuronal apoptosis and long-term behavioural effects using an established mouse model that represents the clinically relevant period of anaesthesia during early infancy in humans. METHODS: Six groups of 10 day old mice (P10) were injected with either etomidate 0.3, 3 or 10 mg/kg, propofol 60 mg/kg, ketamine 50 mg/kg or placebo only. Apoptosis in the cerebral cortex and hippocampus was assessed 24 h after treatment (activated caspase-3). Late behavioural effects were tested at 2 months of age (spontaneous activity in a new environment). RESULTS: No evidence was found of differences in activated caspase 3-concentrations among the study groups. Significant late behavioural changes were only observed in the ketamine group. CONCLUSION: A single dose of etomidate in early infant mice at P10 did not produce evidence of cerebral apoptosis or impaired adult motor behaviour.

Ultrasound-guided peripheral regional anaesthesia: a feasibility study in obese versus normal-weight women.

BACKGROUND AND OBJECTIVES: In particular, obese patients may profit from peripheral regional anaesthesia due to avoidance of general anaesthesia. Currently, ultrasound (US) guidance is described as the golden standard in regional anaesthesia, but no studies have so far evaluated the US behaviour of peripheral nerve structures in obese versus normal-weight patients. To be able to perform such studies, it is necessary to develop new and more objective methods to quantify nerve visibility by US. We therefore designed a prospective, observational, comparative and blinded study to investigate the visibility of peripheral nerves in obese versus normal-weight patients by using a novel method based on histogram grey-scale values. METHODS: We scanned the median and sciatic nerves in 40 obese and normal-weight female patients and calculated differences of histogram grey-scale values between nerves and surrounding tissues. RESULTS: Histogram value analysis showed less US visibility of sciatic nerves in obese versus normal-weight study patients, which is caused by higher surrounding tissue histogram values. No differences could be detected for median nerves. CONCLUSIONS: The novel technique of comparing histogram grey-scale values to determine the visibility of the peripheral nerve in different patient categories was found feasible. Median nerves are appropriately visible by US in both normal and obese subjects, whereas sciatic nerves are less visible in obese as compared with normal-weight women. Our results serve as the rationale behind difficulties in peripheral regional anaesthesia in obese patients.

Reduction of cerebral mean blood flow velocity and oxygenation after high-volume (1.5 ml kg⁻¹) caudal block in infants.

BACKGROUND: We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined 'the CSF rebound mechanism') after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. METHODS: Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (C(R)SO2) were followed during 5 min after the initial caudal injection (1.5 ml kg(-1), ropivacaine 0.2%) in 12 infants <3 months of age. RESULTS: The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation C(R)SO2 was also observed. Systemic haemodynamic parameters were unchanged during the observation period. CONCLUSION: High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to 'the CSF rebound mechanism' for secondary spread of high-volume caudal block.

The use of ultrasound-guided regional anaesthetic techniques in neonates and young infants.

Optimal pain therapy during the perioperative period or at the neonatal intensive care unit and subsequent reduced use of opioids and various sedative drugs is an important factor for patients care. The use of various regional anaesthetic techniques in experienced hands provides excellent pain relief and has the potency to reduce the requirement for perioperative mechanical ventilation. Most of regional anaesthesia techniques are applicable also in neonates and young infants and can be used in an effective and safe manner. Ultrasound guidance should be used for all regional anaesthetic techniques to increase efficacy and safety. The spectrum of indications for ultrasound-guided regional anaesthesia in babies and infants are surgery, selective pain therapy and sympathicolysis. This review reflects an expert-based description of the most recent developments in ultrasound-guided regional anaesthetic techniques in babies and infants.

EEG response to a high volume (1.5 mL/kg) caudal block in infants less than 3 months.

INTRODUCTION: The substantial compression of the dural sac and the subsequent cranial shift of cerebrospinal fluid caused by a high-volume caudal block has been shown to significantly but transiently reduce cerebral blood flow. The aim of the present study was to determine whether this reduction in cerebral perfusion is significant enough to alter brain function, as assessed by electroencephalography (EEG). METHODS: Following ethics approval and parental informed consent, 11 infants (0-3 months) scheduled to undergo inguinal hernia repair were included in the study. EEG electrodes (using nine electrodes according to the 10-20 standard) were applied following anesthesia induction. Following a 5 min baseline period, a caudal block was performed (1.5 mL/kg), whereafter the EEG, hemodynamic, and cerebral near-infrared spectroscopy responses were followed during a 20 min observation period that was divided into four 5 min segments. Special attention was given to alterations in delta power activity since this may indicate cerebral ischemia. RESULTS: All 11 infants displayed transient EEG changes, mainly represented by increased relative delta power, during the initial 5-10 min postinjection. The observed changes had returned close to baseline values 15 min postinjection. Heart rate and blood pressure remained stable throughout the study. CONCLUSION: A high-volume caudal block appears to increase intracranial pressure, thereby reducing cerebral blood flow, to the extent that it transiently will affect cerebral function as assessed by EEG (increased delta power activity) in approximately 90% of small infants. TRIAL REGISTRATION NUMBER: ACTRN12620000420943.

Is there an association between PONV and chemotherapy-induced nausea and vomiting?

BACKGROUND: Drug-induced nausea and vomiting, both post-operatively and following chemotherapy, is often distressing for the patients. Our clinical impression is that certain patients are not prone to but instead protected against both post-operative and chemotherapy-induced nausea and vomiting (CINV). If support for this hypothesis could be generated, it might be easier to identify such patients as low-risk patients and judge all other patients as high-risk patients by default. METHODS: All patients scheduled for breast cancer surgery at Danderyd Hospital, Stockholm, Sweden during 1 year (March 2003-March 2004) were asked to participate in this prospective, observational study. A number of women went on to receive adjuvant chemotherapy. Post-operatively, patients were assessed for 24 h with regard to the occurrence of post-operative nausea and vomiting (PONV). CINV was assessed for 5 days after start of chemotherapy. RESULTS: A total of 275 women were included, 33% were classified as PONV and 67% as non-PONV. Sixty-one of the 275 women included were later subjected to adjuvant chemotherapy. In the non-PONV group, 95% of the patients did not experience CINV, whereas the association between PONV and subsequent CINV was only 38%. CONCLUSIONS: A substantially stronger interrelationship was found between non-PONV and non-CINV than between both PONV and CINV. This may suggest that certain patients, instead of being prone to nausea and vomiting, in fact in some way are protected against these unpleasant side effects.

Secondary spread of caudal block as assessed by ultrasonography.

BACKGROUND: Redistribution and secondary spread after the initial injection of local anaesthetics (LAs) are important factors that contribute to the final spread of caudal block in children. However, to date, these phenomena have yet not been studied in detail. Thus, the aim of this observational study was to define patterns of secondary spread and redistribution of a caudal block by means of real-time ultrasonography scanning and cutaneous testing. METHODS: Ultrasound assessment of LA spread within the caudal-epidural space and epidural pressure was followed during 15 min after initial injection (1.5 ml kg(-1), ropivacaine 0.2%) in 16 infants. At 15 min post-injection, cutaneous testing was also performed to assess the cranial dermatomal level of the block (at end-tidal sevoflurane 2.5%). RESULTS: The median ultrasound-assessed cranial spread was Th10 and Th8 at 0 and 15 min, respectively, and the sensory level at 15 min was Th4. The caudal injection was initially found to compress the terminal part of the dural sac, later followed by a partial re-expansion as epidural pressure was returning towards pre-injection values. An intrasegmental redistribution from the dorsal to the ventral compartment of the epidural space was also observed. CONCLUSIONS: Two separate patterns of secondary spread of caudal block could be observed, being horizontal intrasegmental redistribution and longitudinal cranial spread. The observed bi-directional movement of cerebrospinal fluid (coined 'the CSF rebound mechanism') does explain a major part of the difference between the initial ultrasound-assessed cranial level and the final level determined by cutaneous testing.

Practice advisory on the prevention and management of complications of pediatric regional anesthesia.

STUDY OBJECTIVES: To develop evidence-based recommendations for prevention and management of infections, bleeding, and local anesthetic toxicity in children undergoing regional anesthesia. DESIGN: A joint committee of the European Society of Regional Anesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) studied electronic literature databases of pediatric regional anesthesia to construct evidence-based recommendations. MAIN RESULTS: For epidural anesthesia lumbar or thoracic placement is preferred. Skin preparation prior to block placement with chlorhexidine is preferred to povidone iodine. A tunneled catheter technique is suggested when using the caudal route or if the epidural catheter placement is kept in situ for more than 3 days. Inspection of the epidural catheter insertion site should be performed at least once a day as part of the postoperative management. When medical and physical examination is normal, coagulation tests are usually unnecessary but if coagulation tests are abnormal, neuraxial and deep peripheral nerve blocks are contraindicated. For patients receiving Low Molecular Weight Heparin thromboprophylaxis, a safety interval of two half-lives plus the time required for heparin to reach maximal levels is considered an adequate compromise between bleeding risk and thrombosis risk when removing epidural catheters. Ultrasound-guided peripheral nerve blocks reduce the risk of vascular puncture and thus the risk of local anesthetic toxicity is reduced. CONCLUSIONS: In children undergoing regional anesthesia the incidence of infection, hematoma, and local anesthetic toxicity is low. The ASRA/ESRA joint committee proposes a practice advisory to prevent and treat these complications.

Bilateral thoracic paravertebral block: potential and practice.

Paravertebral nerve blocks (PVBs) can provide excellent intraoperative anaesthetic and postoperative analgesic conditions with less adverse effects and fewer contraindications than central neural blocks. Most published data are related to unilateral PVB, but its potential as a bilateral technique has been demonstrated. Bilateral PVB has been used successfully in the thoracic, abdominal, and pelvic regions, sometimes obviating the need for general anaesthesia. We have reviewed the use of bilateral PVB in association with surgery and chronic pain therapy. This covers 12 published studies with a total of 538 patients, and with varied methods and outcome measures. Despite the need for relatively large doses of local anaesthetics, there are no reports of systemic toxicity. The incidence of complications such as pneumothorax and hypotension is low. More studies on the use of bilateral PVB are required.

Effect of a small priming dose on myoclonic movements after intravenous anaesthesia induction with Etomidate-Lipuro in children.

BACKGROUND: In children, the incidence of injection pain at i.v. anaesthetic induction with Etomidate-Lipuro is low when compared with propofol mixed with lidocaine (5%). However, the incidence of involuntary myoclonic movements (MM) after induction of anaesthesia is higher compared with propofol (85% vs. 15%). In adults, the incidence of MM is reported to be significantly reduced if a small priming dose is administered immediately before the main injection of etomidate. The aim of this prospective, randomized, double-blind, placebo-controlled clinical trial was to investigate if a small priming dose of etomidate effectively can reduce the incidence of MM also in children. METHODS: Eighty ASA I-II children (1-15 yr) were randomized to receive either a small priming dose of etomidate (0.03 mg kg(-1)) or a lipid emulsion placebo. A standardized induction dose of etomidate (0.3 mg kg(-1)) was administered 60 s after the priming dose. The occurrence and severity (observational score 0-3) of MM was defined as the primary endpoint of the study and was recorded during a 2 min period after induction of anaesthesia. A post hoc analysis was performed regarding the incidence of MM with respect to age. RESULTS: No difference in the occurrence or severity of MM was found between the two study groups, the total incidence of MM being 73.8% (95% confidence interval: 62.7-83.0%). The incidence of MM (score > 0) was found to be statistically higher in the age group 5-10 yr compared with <5 yr; and >10 yr (P=0.0008 and 0.01730, respectively). The MM scores were highest in patients aged 5-10 yr (P=0.0021). CONCLUSIONS: Children in the age range of 5-10 yr appear to be especially prone to react with involuntary MM after i.v. induction of anaesthesia with etomidate. The use of a small, non-sedative, priming dose did not influence the incidence of involuntary MM after i.v. induction of anaesthesia with etomidate in children 1-15 yr of age.

Ultrasound assessment of cranial spread during caudal blockade in children: the effect of different volumes of local anaesthetics.

BACKGROUND: Despite the large amount of literature on caudal anaesthesia in children, the issue of volume of local anaesthetics and cranial spread is still not settled. Thus, the aim of the present prospective randomized study was to evaluate the cranial spread of caudally administered local anaesthetics in children by means of real-time ultrasound, with a special focus on the effects of using different volumes of local anaesthetics. METHODS: Seventy-five children, 1 month to 6 yr, undergoing inguinal hernia repair or more distal surgery were randomized to receive a caudal block with 0.7, 1.0, or 1.3 ml kg(-1) ropivacaine. The cranial spread of the local anaesthetic within the spinal canal was assessed by real-time ultrasound scanning; the absolute cranial segmental level and the cranial level relative to the conus medullaris were determined. RESULTS: All the blocks were judged to be clinically successful. A significant correlation was found between the injected volume and the cranial level reached by the local anaesthetic both with regards to the absolute cranial segmental level and the cranial level relative to the conus medullaris. CONCLUSIONS: The main finding of the present study was positive, but numerically small correlation between injected volumes of local anaesthetic and the cranial spread of caudally administered local anaesthetics. Therefore, the prediction of the cranial spread of local anaesthetic, depending on the injected volume of the local anaesthetic, was not possible. EudraCT Number: 2008-007627-40.