bluuebunny/crossref_metadata_2025 huggingface dataset:
Does a local anaesthetic cream (EMLA) alleviate pain from heel‐lancing in neonates?
Authors: LARSSON B. A. , JYLLI L. , LAGERCRANTZ H. , OLSON G. L.
Published: January 2009

EMLA cream is an effective local anaesthetic agent for venipunctures in adults and children. The aim of this double‐blind, randomised, and placebo‐controlled study was to evaluate the effect of EMLA when heel‐lancing was performed in neonates. On their third day of life, fullterm healthy infants, who underwent testing for phenylketonuria (PKU) by heel‐lancing, were consecutively included in the study. One hundred and twelve neonates were allocated to eight groups according to the application time of EMLA or placebo (10 to 120 minutes). Thus in each group seven infants received active substance and seven placebo. The response to the nociceptive stimulation was assessed by studying the occurrence of a pain cry. No analgesic effect of EMLA was found. There were no adverse effects.
Comparison of preoperative with postoperative topical lidocaine spray on pain after tonsillectomy
Authors: ELHAKIM M. , HAY H. ABDEL
Published: January 2009

Seventy‐five children aged 4‐6 years scheduled for tonsillectomy were randomly allocated to receive either topical tonsillar spray with 10% lidocaine 4 mg kg‐1 3 minutes before surgical incision; identical tonsillar spray after both tonsils had been removed; or no topical spray (control group). There were significant differences in postoperative pain between the lidocaine groups and the control group at 0.5 and one hour after awaking (P<0.05). Also in the lidocaine groups, consumption of paracetamol on the day of operation was less, and additional postoperative pethidine was not required. There were no significant differences between pre‐ and postoperative lidocaine groups in pain scores during the observation period but the use of pre‐operative lidocaine tended to be associated with a more rapid return to calm wakefulness. Topical lidocaine seemed to have short‐acting analgesic activity. The results of this study do not support the theory of pre‐emptive analgesia.
Caffeine‐halothane accuracy in MH testing
Authors: HWANG F. , CHUN K. , ANTOGNINI J. F. , GRONERT G. A.
Published: January 2009

The accuracy and stability of caffeine and halothane concentrations in liquid Krebs medium were examined. Caffeine‐Krebs Ringer's solution in incremental concentrations from 0.25 to 10 mM (N=8 for each concentration) was serially assayed over a three‐year period. Storage was at 4°C. For serial testing of halothane during a five month period, halothane 1% or 3% in carbogen was bubbled through a Krebs solution, contained in muscle baths, either using a roller pump (to eliminate vaporizer back pressure) or using carbogen at a line pressure of 4‐6 lbs/in2 (27‐41 kPa). Halothane in Krebs was asssyed by high pressure liquid chromatography. Caffeine concentrations did not vary for 20 weeks. From then, through 60 weeks, concentrations less than 2 mM steadily diminished; after that, through 156 weeks, only 4, 8, and 10 mM were stable. When compared to the halothane concentration in gas entering the muscle baths, halothane concentration in Krebs was predictable regardless of method delivery, as long as a gas analyzer indicated the proper concentration.

We conclude that caffeine solutions are stable for 20 weeks when refrigerated, and for three years at concentrations 4 mM or greater.
Post‐surgery epidural blockade with local anaesthetics attenuates the catecholamine and thermogenic response to perioperative hypothermia
Authors: CARLI F. , KULKARNI P. , WEBSTER J. D. , MACDONALD I. A.
Published: January 2009

Core (aural canal) and mean skin (15 sites) temperatures, plasma adrenaline, noradrenaline and metabolites, and gaseous exchange were measured before, during and for 4 h after surgery in sixteen patients scheduled for elective colorectal surgery. All patients received general anaesthesia and no measures were taken to prevent the perioperative loss of body heat. At time of abdominal wall closure, when the core temperature was below 35.0°C, the patients were randomly allocated to receive either 20‐30 mg of papaveretum i. v. (papaveretum group, n = 8) or 15 ml of bupivacainc 0.75% via thoracic (T9) epidural route to obtain a T4‐S5 sensory blockade (epidural group, n=8). Continuous infusion of either i. v. papaveretum or epidural 0.25% bupivacaine was continued after surgery. During the recovery period of four hours the rate of increase in core and mean skin temperatures was significantly slower in the epidural group compared with the papaveretum group (P<0.01). Plasma catecholamine concentrations remained elevated after surgery in the papaveretum group, whilst they decreased significantly once epidural blockade was established (P<0.001). There was a lower trend, however not significant, in the rise of postoperative oxygen consumption and plasma glucose concentration in the epidural group compared with the papaveretum group.
Intra‐arterial regional anaesthesia for hand surgery with alkalinized 0.5% lignocaine
Authors: KOSCIELNIAK‐NIELSEN Z. J. , STENS‐PEDERSEN H. L. , KJAERBO E. J.
Published: January 2009

Intra‐arterial regional anaesthesia (IARA) for hand surgery is an old, forgotten technique. One of the causes of low popularity may be a scalding sensation in the hand during intra‐arterial injection of lignocaine, which may be caused by low pH of lignocaine's solution.

In this randomized, double‐blind study, normal (pH 5.2‐5.3) or alkalinized (pH 7.2‐7.3) preservative‐free 0.5% lignocaine 1.5 mg kg‐1 was injected into the radial arteries of forty adult patients to produce anaesthesia for ambulatory hand surgery.

Scalding sensation in the hand during intra‐arterial injection (VAS) was less pronounced with alkalinized lignocaine (P=0.04). The time of onset and regression of analgesia was similar in both groups. Four patients in group 1 (normal lignocaine) and six patients in group 2 (alkalinized lignocaine) needed supplemental analgesia at the start of surgery (NS). Cannulation time, operating conditions, motor blockade, surgical‐, and tourniquet pain scores (VAS) and patient's acceptance were similar. Three patients (two in group 1 and one in group 2) had minor systemic adverse effects after tourniquet release (NS). Nine patients in group 1 and seven in group 2 developed minor bruises after cannulation (NS). No other sequelae of intra‐arterial injections were observed.

We conclude that alkalinized 0.5% lignocaine was less painful on injection than normal lignocaine and should be preferred for intra‐arterial regional anaesthesia for hand surgery.
Purine metabolite washout and platelet aggregation at reflow after tourniquet ischemia: effect of intravenous regional lidocaine
Authors: NAESH O. , HALJAMAE H. , SKIELBOE M. , ANDERSEN P. , SZTUK F. , IBSEN A. , HINDBERG I.
Published: January 2009

Tourniquet ischemia will influence the biochemical milieu of tissue cells and affect the metabolism of purines in skeletal muscle distal to the occlusion. At reperfusion, generation of oxygen radicals by the hypoxanthine‐xanthine oxidase system may ensue, influencing white blood cell and thrombocyte aggregation, causing damage to the endothelial cell barrier and inducing non‐reflow type phenomena. Amide‐type local anaesthetics are known to affect local vasotone, leukocyte adherence and platelet function but the influence of lidocaine on purine metabolite washout and platelet aggregation following tourniquet ischemia for lower limb surgery is not known in detail. Therefore, the effects of regional intravenous lidocaine during tourniquet ischemia for knee surgery on purine catabolite washout and platelet function following reflow were assessed.

Eight patients served as control (G‐group) and 8 (L‐group) received 100 ml of lidocaine (2.5 mg/ml) in the emptied venous bed of the leg to be operated. All patients had spinal anaesthesia (0.5% bupivacainc). Effluent venous blood from the leg and radial arterial blood was collected and analysed for xanthine (X), hypoxanthine (HX), base excess (BE), pH and potassium before and after reperfusion. Platelet ADP‐induced aggregation (ADP‐agg.) and secretion of beta‐thromboglobulin (β‐TG) were measured in the effluent blood as well as systemically. After tourniquet release (TR), X and HX were significantly increased in effluent venous blood but the washout was enhanced in the L‐group during the initial reperfusion phase. BE was significantly higher in the L‐group both before and after TR whereas pH and potassium washout was comparable between the groups. No systemic effects on platelets were detected after tourniquet release but ADP‐agg. in effluent venous blood was attenuated in 6 out of 8 patients in the L‐group (NS).

It is concluded that HX and X are generated during leg ischemia. Regional intravenous lidocaine, most probablythrough a vasodilatory mechanism and inhibition of white blood cell activation, may attenuate non‐reflow phenomena and thereby exert beneficial effects on post‐ischemic recovery by enhancing post‐ischemic tissue reperfusion.
Autotransfusion after open heart surgery: quality of shed mediastinal blood compared to banked blood
Authors: SCHMIDT H. , KONGSGAARD U. E. , GEIRAN O. , BROSSTAD F.
Published: January 2009

The need to conserve a patient's own blood and avoid homologous transfusion is now well recognized. Therefore, techniques designed to reduce requirements for homologous blood transfusions have been developed. One of the methods is autotransfusion of shed mediastinal blood after open‐heart surgery. The objectives of the present study were to investigate osmotic fragility and oxygen transport capacity of shed mediastinal blood compared to patient blood and stored packed red blood cells (SAGM).

Shed mediastinal blood from ten consecutive patients undergoing elective cardiac surgery (coronary bypass grafting) was studied and compared to patient blood, 10 units of 3 weeks old and 10 units of 5 weeks old stored packed red blood cells (SAGM). Oxygen transport capacity was investigated by calculation of p50 for oxygen by use of the oxygen status algorithm (OSA 2.0) programme and measurement of 2,3‐diphosphoglycerate (2,3‐DPG) concentrations. The osmotic fragility was determined using increasing concentrations of saline.

2,3‐DPG concentrations in shed mediastinal blood (5,3 mikromol/ml erythrocyte) were within the range measured in patient blood, but significantly higher than SAGM blood (P<0.001). P50 for oxygen (3.5 kPa) in shed mediastinal blood was not significantly different compared to patient blood, but significantly higher (P<0.01) compared with stored SAGM blood. The osmotic fragility in shed mediastinal blood was not significantly different compared to patient blood, but significantly lower (P<0.001) than the osmotic fragility in stored SAGM blood. This suggests that red cells saved from shed mediastinal blood have better oxygen transport capacity and may have longer survival compared to stored blood.
Direct cadiac electorphysiologic effects of sufentanil and vecuronium in isolated guinea‐pig hearts
Authors: Weber G. , Stark G. , Stark U.
Published: January 2009

Sufentanil and vecuronium are commonly used simultaneously in anaesthesia. Bradycardia and asystole have been described immediately after the administration of these two compounds. Therefore, the purpose of the present study was to evaluate the direct cardiac effects of sufentanil and vecuronium in all parts of the cardiac pacemaker and conduction system.

The electrophysiological effects of sufentanil and vecuronium were studied in isolated spontaneously beating guinea‐pig hearts perfused by the method of Langendorff. At a concentration of 0.1 μmol/1 sufentanil a significant reduction of the spontaneous sinus rate, prolongation of atrioventricular, intraventricular and His' bundle conduction could be observed. The highest concentration of 10 μmol/1 of sufentanil led to an overall slowing of conduction velocity and to an profound slowing of spontaneous sinus rate. AV nodal as well as atrial and ventricular refractoriness were markedly prolonged at this high concentration of sufentanil. In contrast, during perfusion with vecuronium at a concentration of 0.1 μmol/1 up to 10 μmol/1 no significant effects on cardiac conduction and pacemaker activity could be observed.

In conclusion, the electrophysiological effects of sufentanil are comparable to that of unspecific calcium antagonists. Therefore, especially in patients with a preexisting damage of the cardiac conduction system, the indirect effect of the combination of sufentanil and vecuronium which is predominantly responsible for bradycardia and asystole may be worsened by the direct effects of sufentanil.
Do changes in carhiac output affect the inspiratory to end‐tidal oxygen dfference?
Authors: BENGTSSON J. , EDERBERG S. , STENQVIST O. , BENCTSO J. P.
Published: January 2009

Background. The paramagnetic technique has made it possible to monitor the end‐tidal oxygen concentration and P(I‐ET)O2, i. e. inspiratory to end‐tidal oxygen difference, breath‐by‐breath. Little is known about the implications of a changing P(I‐ET)O2, but so far studies have shown it to be a quick and sensitive variable to detect hypoventilation. This study was designed to observe the circulatory effects on P(I‐ET)O2 in an experimental setting but monitored as in a clinical situation.

Methods. We assessed the oxygen difference during changes in cardiac output induced by intravenous ephedrine‐hydrochloride in 12 healthy male volunteers. P(I‐ET)O2 was measured with a fast‐response paramagnetic differential oxygen sensor. Cardiac output was measured with non‐invasive transthoracie electrical bioimpedance. As stimultaneous changes in metabolism and ventilation will also influence P(I‐ET)O2, oxygen uptake and expired minute volume were monitored. After a rest period, the subjects had an intravenous injection of ephedrine‐hydrochloride 0.1 mg·kg‐1 followed by a 30‐min observation period.

Results. Cardiac output increased significantly as did the oxygen uptake and the ventilation. We found no biologically significant correlation between cardiac output and P(I‐ET)O2. The P(I‐ET)O2 was influenced by ventilation and metabolism.
Effects of ephedrine on oxygen consumption and cardiac output
Authors: RADSTROM M. , BENGTSSON J. , EDERBERG S. , BENGTSSON A. , LOSWICK A. C. , BENGTSON J. P.
Published: January 2009

Bolus doses of ephedrine are often used by anaesthesiologists for intraoperative hypotension. This randomized single‐blind cross‐over study was designed to simultaneously evaluate circulatory, respiratory and metabolic effects of intravenously given ephedrine in 12 healthy male volunteers. Oxygen uptake and carbon dioxide excretion were measured with indirect calorimetry and non‐invasive transthoracic electrical bioimpedance was used for cardiac output measurements. The maximum effect on most variables was reached at 4‐5 min. At 5 min after the administration of ephedrine 0.1 mg per kilogram body weight, there were significant increases in cardiac index, systolic and mean arterial blood pressure, expired minute volume, oxygen uptake and carbon dioxide excretion rates. There were no significant changes in the quotient between oxygen uptake rate and cardiac index, VO2/CI during the 30 min study period. The O2 saturation was not altered. The present study indicates that ephedrine increases oxygen demand and supply in a similar magnitude.
Effect of continuous positive airway pressure (CPAP) in patients with chronic obstructive pulmonary chsease (COPD) depending on intrinsic PEEP levels
Authors: BERG B. VAN DEN , AERTS J. G. J. V. , BOCAARD J. M.
Published: January 2009

The application of continuous positive airway pressure (CPAP) is known to reduce inspiratory work of breathing in intubated patients with chronic obstructive pulmonary disease (COPD). This effect is caused by a decrease in elastic work related to a reduction in intrinsic PEEP. The aim of this study was to relate the decrease in inspiratory work due to CPAP to the intrinsic PEEP levels obtained during spontaneous breathing without positive pressure. Ten intubated patients with COPD who had been ventilated for acute respiratory failure were studied. Intrinsic PEEP was determined during tracheal occlusions performed at end‐expiration when the patient was breathing without positive airway pressure. Inspiratory work was computed during breathing through a circuit with a CPAP of 0.5 kPa and the same circuit without positive pressure. Intrinsic PEEP‐levels ranged from 0.26 to 1.31 kPa. Compared to spontaneous breathing without positive pressure, CPAP reduced the total inspiratory work per liter of ventilation (Wltot) from 1.42±0.48 to 1.24±0.50 J·1‐1 (means±SD P<0.01). This decrease was found to be related to the intrinsic PEEP‐levels: the largest reductions were found in the patients with an intrinsic PEEP‐level close to the CPAP‐level applied. In intubated patients with COPD, the decrease in Wltot due to a CPAP of 0.5 kPa was found to be related to the intrinsic PEEP‐levels present when no positive airway pressure was applied. The intrinsic PEEP measured during tracheal occlusions could be used to estimate the effect of CPAP in these patients.
Comparison of propofol and increased doses of thiopentone for laryngeal mask insertion
Authors: BROWN G. W. , ELLIS F. R.
Published: January 2009

Conditions for insertion of the laryngeal mask were assessed following induction of anaesthesia with either propofol 2.5 mg/kg, thiopentone 5.0 mg/kg or thiopentone 6.0 mg/kg in 120 patients premedicated with diazepam 10 mg. Insertion following induction with thiopentone 5.0 mg/kg and 6.0 mg/kg resulted in a greater incidence of gagging (P<0.001 and P<0.05, respectively) compared with propofol 2.5 mg/kg.
Effects of halothane and isoflurane on antigen‐ and leukotriene‐D4‐induced constriction of guinea pig trachea
Authors: TUDORIC N. , COON R. L. , KAMPINE J. P. , BOSNJAK Z. J.
Published: January 2009

We investigated the mechanism of the action of volatile anesthetics on the airway smooth muscle constricted by an antigen and leukotriene‐D4(LTD4).

Excised tracheal rings from ovalbumin‐sensitized guinea pigs were suspended in eight tissue baths. Halothane or isoflurane was aerated into four tissue baths, while the remaining four served as time controls. To assess the antispasmogenic activity of halothane and isoflurane, concentration‐response curves for antigen and LTD4were constructed exposed to anesthetics and compared to controls. The spasmolytic activity of halothane and isoflurane was measured in the tracheal rings constricted by a single antigen challenge or by EC50of LTD4.

Both halothane and isoflurane produced significant rightward shifts of ovalbumin and LTD4concentrationresponse curve with corresponding increases in the EC50values. Halothane increased the EC50value for LTD1from 5.38±0.43×10‐9M to 1.2±0.18×10‐8M, and for ovalbumin from 1.2±0.06×10‐4mg/ml to 3.03±0.28×10‐4mg/ml. Isoflurane increased the EC50value for LTD4from 5.17±0.64×10‐9M to 8.98±1.01×10‐9M, and for ovalbumin from 1.21±0.09×10‐4mg/ml to 2.61±0.19×10‐4mg/ml. Furthermore, halothane and isoflurane significantly reduced the magnitude of antigen‐and LTD4‐induced constriction. In 30 min intervals, 1% and 2% halothane reduced the magnitude of the ovalbumin‐induced constriction by 32% and 50%, respectively, while isoflurane (2% and 4%) caused relaxation of 16% and 35%, respectively. The magnitude of LTD4‐induced constriction was reduced by 17% and 24%, with 1% and 2% halothane, respectively. Isoflurane (2% and 4%) reduced this constriction by 25% and 25%, respectively.

In conclusion, halothane and isoflurane attenuate and prevent the constrictive response of airway smooth muscle to allergen and LTD4. A direct, nonspecific dilating effect is suggested as the mechanism responsible for the observed effects.
Hyperkalaemia associated with haemorrhagic shock in rabbits: mochfication by succinylcholine, vecuroniurn and blood transfusion
Authors: ANTOCNINI J. F. , MARK K.
Published: January 2009

In haemorrhagic patients, hyperkalaemia may occur after succinylcholine administration. We investigated in haemorrhagic rabbits whether vecuronium caused hyperkaelemia and if blood transfusion prevented succinylcholine‐induced hyperkalaemia.

Rabbits were lightly anaesthetized with halothane/N2O and 30‐35 ml/kg blood were withdrawn to cause arterial pH to decrease to ∼ 7.0‐7.1. Group C (n = 12) received 3 ml saline, Group S (n = 13) received succinylcholine lmg/kg. Group V (n = 7) received vecuronium 0.25 mg/kg and Group T (n = 9) was transfused with 10 ml/kg blood 10 min prior to receiving succinylcholine 1 mg/kg. K+ analysis was repeated at 5 min, and at 10 min in most animals.

Haemorrhage increased K+ (mmol·1‐1, mean ± SD): Group C, 3.4±0.3 to 6.8±1.8; Group S, 3.8±0.5 to 6.9±2.3; Group V, 3.8±0.3 to 7.1±1.9; Group T, 3.6±0.5 to 7.6±2.9. K+ decreased in Group T (to 5.4±1.8) after blood transfusion. K+ increased at 5 min in Group S (to 8.7±2.6) and at 10 min for Group C (to 8.4±1.7) and Group T (to 7.2±2.3). The K+ increase at 5 min for Group S (1.8±0.8) was significantly higher than those for Group C (1.0±0.6) or Group V (0.9±0.4), but was not different from that of Group T (1.5±0.7).

We conclude that haemorrhage and succinylcholine cause hyperkalaemia in rabbits. Muscle relaxation itself does not appear to be a factor, but transfusion may lessen the hyperkalaemia.
Management of a spinal catheter that became in tr avas cular
Authors: GAGGERO G. , VAN GESSEL E. F. , GAMULIN Z.
Published: January 2009

The management of a misplaced spinal catheter in an 83‐year‐old women undergoing elective knee surgery, in whom clear cerebrospinal fluid and blood were alternately aspirated through the catheter during the surgical procedure, is described. In the face of catheter misplacement, before administering general anesthesia, the authors recommend using a small “test dose” of local anesthetic to confirm subarachnoid location of catheter despite lack of frank reflux of cerebrospinal fluid.
Report of two cases
Authors: LIU K. , CHIA Y.‐Y.
Published: January 2009

Two patients underwent thoracotomy for resection of pulmonary or esophageal carcinoma. Postoperatively, epidural catheters were inserted for pain management. Complaints of severe injection pain over the abdomen or lower extremities were made during one administration of pain medication. Progressive weakness and numbness developed over the lower trunk and lower extremities, with subsequent respiratory difficulties. Potassium chloride (KCl) was suspected to have been mistaken for normal saline as the diluent for morphine. In addition to endotracheal intubation and ventilatory support, steroids were administered both intravenously and epidurally to suppress spinal cord irritation. The two patients regained motor and sensory functions 14 and 18 hours later, respectively, without sequelae.
From in vitro to in vivo monitoring
Authors: SIGGAARD‐ANDERSEN O. , GØTHGEN I. H. , FOGH‐ANDERSEN N.
Published: January 2009

In vitro monitoring is inherently invasive with discrete measurements on blood samples and the results are often delayed an hour or more when the analyses are performed in the central laboratory. The delay may be greatly reduced if the analyses are performed near the patient. In vivo monitoring may be non‐invasive and may provide continuous real‐time data but the accuracy usually does not match that of in vitro measurements. In vivo monitoring therefore finds its application in the detection of trends of change, and it is needed only for quantities that change rapidly and unpredictably and where a suitable therapeutic action is available. In critically ill patients, this applies to the arterial pO2, pCO2, and pH, and the mixed venous pO2. Ideal in vivo monitoring techniques are not available for all these quantities. In the newborn, the arterial pO2 may be monitored with a transcutaneous pO2 electrode. In the adult, the arterial pO2 may be monitored indirectly by monitoring the arterial oxygen saturation with a pulse oximeter and the mixed venous pO2 by monitoring the mixed venous oxygen saturation with a catheter tip sensor. The arterial pCO2 may be monitored with a transcutaneous pCO2 electrode or by capnography, i. e., by monitoring the end‐expiratory pCO2. Other in vivo monitoring techniques such as gastric tonometry for the gastric mucosal pH and thoracic impedance measurement have found some routine application, whereas near‐infrared spectrometry for oxy‐ and deoxyhaemoglobin in the brain, and magnetic resonance spectroscopy for tissue ATP are at the stage of research and development.
Electrochemical sensors for continuous monitoring during surgery and intensive care
Authors: TURNER A. P. F.
Published: January 2009

The current state of development of electrochemical sensors and biosensors for continuous use during surgery and intensive care is briefly reviewed with an emphasis on recent developments. The clinical usefulness of invasive and non‐invasive sensors is discussed. Recent advances in the design of electrochemical sensors and experience with ex vivo and in vivo applications are described. The importance of developing appropriate fabrication technology is emphasised in order to meet the demand for reliable and reproducible analytical devices.
Continuous in vivo monitoring in diabetes: the subcutaneous glucose concentration
Authors: FISCHER U.
Published: January 2009

The most advanced glucose sensors are measuring amperometrically the hydrogen peroxide generated in a stoichiometric relation to the prevailing glucose concentration during glucose oxidase‐mediated glucose oxidation. They proved useful in commercially available glucose analysers and in experimental subcutaneous (sc) monitoring. Here it is shown (a) that under steady state conditions the sc. glucose concentration is nearly identical to that in blood, (b) that sc. inserted glucose electrodes do mirror the intracorporal glucose concentration both under hypo‐, normo‐, and hyperglycaemic conditions with a clinically relevant accuracy, (c) that automated feedback control of intracorporal glucose concentration is possible applying the output of sc. glucose sensor as an input to the computer that controls the insulin pump, and (d) that stable function of sc. sensor may be accomplished over intervals up to one day; in some cases applications over up to ten days have been reported. The underlying problem consists in an insufficient functional biostability which is a function of biocompatibility and size of the sensor, of its sterility, and of the permanent skin penetration. The latter is still required to get the device in place, to keep it in function, and to make use of the data under any condition. At this time, sc. glucose electrodes to be employed as hypoglycaemia‐warning systems over one day are considered clinically important and technically achievable.
Bio‐/haemocompatibility: implications and outcomes for sensors?
Authors: KYROLAINEN M. , RIGSBY P. , EDDY S. , VADGAMA P.
Published: January 2009

Sensors are a sample contacting technology, and when exposed to biological matrices tend to suffer from the problem of poor biocompatibility and surface fouling. The effects are evidenced by time dependant signal drift (particularly for those devices which are implanted intravascularly). Practical methods to reduce such effects require an understanding of the interface between the electrode and its environment prior to assessment of the potential areas for improvement. Current procedures employed to overcome the observed losses in electrode sensitivity (following exposure to whole blood) include surface modification of the outer diffusion limiting membrane (via variation in film porosity) or even biomimicry of the fluid cell membrane. At amperometric electrodes incorporation of additional inner perm‐selective membranes has achieved a reduction in electrode passivation from undesirable surface active compounds as has the use of low polarisation potentials. Other studies have attempted to induce an aqueous barrier between the matrix and the electrode tip which physically prevents passage of cellular components from the sensor surface.

Careful choice of the system and materials will ultimately lead to biocompatible non‐fouling devices capable of functioning in an array of bio‐environments suitable for clinical monitoring of the critically ill patient.
Intra‐arterial and extra‐arterial pH, PCO2 and PO2 monitors
Authors: SHAPIRO B. A.
Published: January 2009

In vitro blood gas analysers inherently limit the frequency of serial blood gas measurements because of blood loss and cost. In vivo blood gas monitors eliminate an inherent cost and blood loss associated with measurement. Optode microsensing is a technology that can be readily adapted to in vivo measurement of pH, PCO2 and PO2. Optode‐based intra‐arterial devices that display continuous values have been developed that are practical for routine use but consistent performance remains a problem; an extra‐arterial device that provides intermittent values has been shown to be consistent but is not yet available for routine use. The transfer of blood gas measurements from laboratory analysers to the combination of point‐of‐care analysers and monitors should have as profound an impact on acute respiratory care as did the introduction of laboratory‐based blood gas analysers over 30 years ago. However, we must be sure these devices are reliable, consistent and cost beneficial in order to avoid widespread adoption of yet another technology that provides more data, more cost, and questionable patient benefit.
Muscle relaxants and histamine release
Authors: Moss J.
Published: January 2009

Many anaesthetic drugs and adjuvants can cause the release of histamine by chemical (anaphylactoid) or immunologic (anaphylactic) mechanisms. While both types of reactions can be clinically indistinguishable, they are mechanistically different. In anaphylactoid reactions, only preformed mediators are released, of which histamine may be the most clinically important. In true immunologic reactions, mast cell degranulation occurs, and many vasoactive substances (including histamine) are released. Clinical signs and symptoms of both classes of reactions include hypotension (most common), tachycardia, bronchospasm, or cutaneous manifestations. Anaphylactoid reactions may occur commonly under anaesthesia in response to many drugs, including induction agents, some opiates, plasma expanders, and curariform relaxants. Anaphylactic reactions are far less common than anaphylactoid reactions, but they nevertheless represent more than half of the life‐threatening reactions that occur in anaesthetic practice. Muscle relaxants are the most frequently implicated class of drugs; suxamethonium is the most common agent implicated in anaphylactic reactions during anaesthesia, but even drugs without apparent chemical histamine release (i. e., vecuronium) are frequently implicated in anaphylactic reactions.
Mivacurium chloride—a comparative profile
Authors: DIEFENBACH C. , BUZELLO W. , MELLINGHOFF H.
Published: January 2009

Mivacurium is a new nondepolarizing muscle relaxant of the benzylisoquinoline type. Its short duration of action is due to rapid breakdown by plasma cholinesterase. The dose of mivacurium which produces 95% inhibition of twitch response (ED95) is between 60 and 80 μg/kg. Thus, mivacurium is 0.8 times and four times as potent as vecuronium and atracurium, respectively. With 2–3×ED95, tracheal intubation can be accomplished within 2.5 min of intravenous injection. The ensuing DUR25% (time from injection to 25% recovery of control twitch tension) is twice as long as with suxamethonium and about half as long as with equipotent doses of atracurium or vecuronium. For muscle relaxation during long surgical procedures, mivacurium has been used as a continuous infusion. The average 6‐min recovery index after infusion of mivacurium is particularly favourable for flexible control of muscle paralysis, whereas the recovery indices after infusion of atracurium or vecuronium are 15–30 min. In conclusion, mivacurium will close the pharmacodynamic gap between suxamethonium and the nondepolarizing muscle relaxants of intermediate duration of action. It will probably also be a suitable alternative to suxamethonium in elective cases.
Comparison of the neuromuscular effects of mivacurium and suxamethonium in infants and children
Authors: COOK D. R. , GRONERT B. J. , WOELFEL S. K.
Published: January 2009

We compared both the time course of neuromuscular blockade and the cardiovascular side‐effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2–12 months and children 1–12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2×ED95 was used in four groups of infants and children, while 3.4×ED95 was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium (P=0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min (P×0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4×ED95 did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T25) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively (P×0.05). In children given 3.4×ED95 of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2×ED95, with spontaneous recovery to T25 prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.
Mivacurium chloride administration by infusion
Authors: APFELBAUM J. L.
Published: January 2009

As a consequence of its rapid hydrolysis by plasma cholinesterase, mivacurium has a short duration of action, and recovery from neuromuscular blockade is rapid (5–95% twitch recovery= 13–15 min). Mivacurium is easy to titrate to individual patient requirements; the average infusion rate to maintain neuromuscular blockade at 89–99% twitch suppression during N2O/opioid anaesthesia is 6–7 μg/kg per min in adults and approximately 14 μg/kg per min in children. There is no evidence of a cumulative effect of mivacurium; recovery is unaffected by dose administered or duration of infusion. These characteristics make mivacurium a very suitable agent for use by infusion.
Spontaneous recovery or evoked reversal of neuromuscular block
Authors: MIRAKHUR R. K.
Published: January 2009

Recovery from the effects of muscle relaxants can occur either spontaneously by their metabolism in the body or by elimination via the normal excretion pathways, or by the administration of pharmacologic antagonists. The decision as to whether spontaneous recovery should be allowed to take place or pharmacologic reversal should be induced depends upon several factors, principal among them being the duration of action of the muscle relaxant used, its dose, and the time that is available. The recovery times of most relaxants, including atracurium and vecuronium, are such as to require antagonism if adequate recovery is to be attained quickly. An agent such as mivacurium may, however, allow complete spontaneous recovery to take place without the use of antagonists.
Effect of neostigmine at different levels of mivacurium‐induced neuromuscular blockade
Authors: TRÉEAVIEN V. , LIENHART A. , JUST B. , CHANDON M. , BARAS E. , CAMATTE S.
Published: January 2009

The effectiveness of neostigmine 40 μg/kg for antagonism of two different levels of neuromuscular blockade, induced by a bolus dose of mivacurium 0.15 mg/kg, was studied in 45 patients. The patients were anaesthetized with thiopentone, fentanyl, nitrous oxide in oxygen, and enflurane. Neostigmine was administered at either 10% recovery of the twitch height (TH10) at the adductor pollicis muscle (n=14) or upon reappearance of the first response at the orbicularis oculi muscle (OO1) after train‐of‐four (TOF) stimulation (n= 16), the latter representing a deeper degree of neuromuscular blockade. Fifteen of the 45 patients did not receive neostigmine (control group). Neostigmine administration at OO1 rather than at TH10 at the adductor pollicis muscle caused reversal of neuromuscular blockade to occur 8 min earlier and shortened the time to reach 25% recovery of the twitch height (TH25) at the adductor pollicis muscle by about 5 min, compared with the control group. However, the time needed to reach a T4/T1 ratio ≥0.8 was similar in both the early and late neostigmine administration groups, being 9 min faster than in the control group. It can be concluded that there is no advantage in administering neostigmine at profound neuromuscular blockade to achieve clinically adequate recovery (T4/T1 ratio ≥0.8). However, the time between injection of mivacurium and TH25 may be shortened by using neostigmine at profound neuromuscular blockade, a procedure which may be useful in case of unpredictably difficult intubation, since diaphragmatic movements usually reappear at TH25.
Isomerism and anaesthetic drugs
Authors: CALVEY T. N.
Published: January 2009

Isomers are two or more different substances with the same molecular formula (i. e., the same number of different types of atoms). There are two main types of isomerism: 1) structural isomerism, and 2) stereoisomerism. Structural isomers (e. g., enflurane and isoflurane) have different molecular structures, and usually behave like different drugs. Occasionally, structural isomers are interconvertible (i. e., they are tautomers or dynamic isomers); this occurs with the barbiturates and midazolam. Stereoisomers have identical structures, but a different configuration or spatial arrangement. Stereoisomerism in drugs is often due to chirality or “handedness”; i. e., the presence of right‐handed (R)‐ and left‐handed (S)‐ forms of drugs which are nonsuperimposable mirror images (“enantiomers”). Approximately 60% of anaesthetic agents are chiral drugs; some of these are administered as single enantiomers. However, many synthetic chiral drugs are equal mixtures of (R)‐ and (S)‐isomers, and there are often important differences in their activity and pharmacokinetics. Halothane, enflurane, and isoflurane are chiral drugs with different anaesthetic potencies. Similar differences occur with intravenous anaesthetics; thus, (S) (+)‐ketamine causes fewer psychotic emergence reactions, less agitated behaviour, and better intraoperative amnesia and analgesia than its enantiomer. Some local anaesthetics are administered as chiral mixtures; the (S)‐isomers have a longer action because of enhanced vasoconstriction. (S)‐prilocaine is more slowly metabolized than its enantiomer, while (S)‐bupivacaine may produce less cardiotoxicity than (R)‐bupivacaine. These differences suggest that some anaesthetic drugs (particularly ketamine and chiral local anaesthetics) should be administered as single enantiomers. In recent years, their synthesis has been greatly simplified, and almost all new drugs may soon be introduced in this form. At present, atracurium consists of 10 stereoisomers, which have different activities and pharmacokinetic properties; however, studies of the related compound norcoralydine suggest that the single isomer with the (R)‐cis‐(R)‐cisconfiguration may produce the best neuromuscular blockade.
Pharmacokinetics of 51W89: preliminary data
Authors: HUNTER J. M. , EASTWOOD N. B. , BOYD A. H. , PARKER C. J. R.
Published: January 2009

The pharmacokinetics of the 1R cis‐1'R cis‐isomer of atracurium (51W89) and its metabolite, laudanosine, were studied in 11 healthy patients with normal renal function and in 12 patients with chronic renal failure undergoing regular dialysis. A bolus dose of 51W89 (0.1 mg/kg) was given, and the plasma concentration was measured at regular intervals for 480 min. The elimination half‐life of 51W89 was significantly longer in renal failure patients than in healthy controls (38.9 min vs 30.6 min; P(0.05). The plasma laudanosine levels were lower than those reported after an equipotent dose of atracurium besylate. 51W89 may have a prolonged effect in renal failure patients.
Central venous versus mixed venous oxygen content
Authors: FABER T.
Published: January 2009

Mixed venous oxygen content (commonly measured as oxygen saturation) is a highly relevant parameter in the monitoring of critically ill patients; unfortunately, its measurement requires catheterization of the pulmonary artery. Though less invasive, the central venous oxygen saturation is an unsatisfactory substitute, due to fluctuations in perfusion distribution and regional oxygen extraction in the course of illness.

The present study examined the relation of oxygen contents in simultaneously withdrawn central venous and mixed venous blood samples from critically ill patients, in order to validate a hypothetical algorithm for the estimation of mixed venous oxygen content from a central venous sample: Although the proposed algorithm had a fairly high power of prediction, its merits in comparison to assuming simple proportionality between central venous and mixed venous oxygen content seemed marginal.

However, as it is likely that the results so far are mathematically coupled, further prospective studies are necessary.
Indicators of histohypoxia
Authors: WILLIS N. , MOGRIDGE J.
Published: January 2009

Cellular tissue damage due to inadequate oxygen supply is frequently encountered in the critically ill patient and can be the end result of a number of conditions. The eventual disruption to the normal processes required for the cell to survive can be due either to the hypoxic state per se or by damage caused during reperfusion of the tissue.

Blood gas analysis is commonly used as a macro indicator of oxygen supply, state of art blood gas analysers provide information for oxygen tension (pO2), haemoglobin oxygen saturation (SO2) and concentration (THb), ideally, in arterial and mixed venous blood.

The concurrent measurement of carbon dioxide tension (pCO2) and pH will allow the calculation of variables which assist in differentiating between respiratory and non‐respiratory conditions.

Measurement of cardiac output and clinical assessment of the patients' oxygen requirements will complete the macro picture of supply and demand and although computed indicators of hypoxia have been improved in recent years (1, 2) the definitive diagnosis of histohypoxia requires the measurement of the cellular and subcellular products of metabolic processes that are present when an inappropriate concentration of oxygen has been experienced.

However, increases, for example, in blood lactate concentration can occur when an ischaemic area is reperfused and it is argued conversely, that the absence of hyperlactataemia in conditions such as acute respiratory distress syndrome does not necessarily preclude delivery dependence of oxygen consumption with the attendant potential for tissue hypoxia (3). Nevertheless there is general agreement that blood lactate levels can serve as a reliable clinical guide to therapy (4).

The laboratory measurement of the metabolic products that accumulate when cellular oxygen supply is limited has become far less labour intensive and with the development of increasingly sophisticated instrumentation, these analytes can be available in small to medium hospital laboratories as well as the larger units.

The relatively rapid and accurate analysis of metabolites that accumulate in hypoxic states has allowed us to measure concentrations of blood lactate, pyruvate, β‐hydroxybutyrate and acetoacetate and calculate the lactate/pyruvate ratio and β‐hydroxybutyrate/acetoacetate ratio.

These measurements and ratios can then be compared with the non invasive macro blood gas indicators in order to determine their effectiveness as additional “routine” investigations and to indicate how each of the variables contributes to the eventual diagnosis.

The parameters used in this study are as follows:

Oxygen tension ‐ pO2,

Haemoglobin oxygen saturation ‐ SaO2

Haemoglobin concentration ‐ THb

Hydrogen ion concentration as ‐ pH

Concentration of extractable oxygen ‐ Cx

Oxygen extraction tension ‐ px

Conditional extraction at an assumed pvO2 = 30 mmHg ‐ C(a‐30)O2

Lactate and pyruvate

β‐hydroxybutyrate and acetoacetate
Notes on the apparent discordance of pulse oximetry and multi‐wavelength haemoglobin photometry
Authors: NIJLAND R. , JONGSMA H. W. , NlJHUIS J. G. , OESEBURG B. , ZlJLSTRA W. G.
Published: January 2009

Multi‐wavelength photometers, blood gas analysers and pulse oximeters are widely used to measure various oxygen‐related quantities. The definitions of these quantities are not always correct. This paper gives insight in the various definitions for oxygen quantities. Furthermore, the possible influences of dyshaemoglobins and fetal haemoglobin on the accuracy of pulse oximetry are discussed.

As pulse oximeters are constructed for the determination of arterial oxygen saturation, they should be validated with sample oxygen saturation values and not with the oxyhaemoglobin fraction. The influence of carboxy‐haemoglobin is insubstantial over an oxygen saturation range of 0% to 100%. Through the presence of methaemoglobin, pulse oximetry will give an underestimation above 70% and an overestimation below 70% oxygen saturation. The influence of fetal haemoglobin is insignificant in the neonatal use of pulse oximetry, in the range of 75% to 100% arterial oxygen saturation. However, a pulse oximeter underestimates the arterial oxygen saturation at the 25% level with 5%, if the pulse oximeter has been calibrated in human adults. Such a low level of arterial oxygen saturation can be present in the fetus during labor.
Preliminary evaluation of a new continuous intra‐arterial blood gas monitoring device
Authors: PAPPERT D. , ROSSAINT R. , LEWANDOWSKI K. , KUHLEN R. , GERLACH H. , FALKE K. J.
Published: January 2009

Continuous intra‐arterial blood gas monitoring is a new technique, possibly offering therapeutic advantages through improved monitoring in patients prone to hypoxaemia, hypercapnia and/or respiratory acidosis. Therefore, we studied the clinical applicability, reliability, precision and side effect of long‐term continuous intraarterial blood gas monitoring in patients suffering from severe acute respiratory distress syndrome.

In 10 patients continuous intra‐arterial blood gas monitoring based on fluorescent optodes technique was performed. At 4 h intervals, arterial blood samples for in vitro blood gas analyses were drawn, stored in ice, and analysed within 3 min. Evaluation of data retrieved from the continuous intra‐arterial blood gas monitoring and in vitro blood gas analysis was based on 596 data points using 10 catheters. Average length of insertion was 281±215 h, max. lengths of stay was 750 h. Arterial blood gas data obtained in vivo were compared to the mean of in vivo and in vitro arterial blood gases.

Inter‐catheter bias, expressed as percent difference between continuous intra‐arterial blood gas and mean in vitro blood gas analysis was 0. 19±0. 23% for pH, 1. 1 ±5. 2% for PaCO2 and 1. 6±5. 7% for PaO2. No significant gas partial pressure dependent change in precision was demonstrable. There was no significant time dependent drift in sensor precision over the study period. No negative side‐effects related to IABG monitoring were observed.

We conclude that long‐term use of this new device is possible in patients and represents a reliable alternative to conventional in vitro arterial blood gas analysis, when continuous monitoring of blood gases and/or acid‐base balance is critical.