Monitoring during paediatric cardiac anaesthesia

Monitoring of paediatric anaesthesia has become increasingly more complex in recent years and this is particulary true of cardiac anaesthesia. The purpose of this review is to give a comprehensive update of published material related to both routine and specialized cardiac monitoring. Routine monitoring can be particularly affected by the alterations of cardiac rhythm, blood flow, cardiac output and oxygenation which result from the congenital heart abnormalities themselves, the type of surgery undertaken and the effects of cardiopulmonary bypass. The use of specialized monitoring is becoming more widespread, particularly in the areas of cerebral function, mixed venous oxygenation, cardiac output measurement and coagulation. In the last five years, with the development of smaller probes, a great deal has been published on transoesophageal echocardiography. The use of the current monitors of cerebral function still remains controversial despite the need for a monitor of adequate brain perfusion, reflecting the need for a great deal of further research in this area. This review will concentrate on particular areas which have seen the most profound changes and on monitoring that may form the standards of tomorrow. Finally, amongst all the technology, it should not be forgotten that the most important clinical monitor is the bedside clinical monitoring of the physicians themselves. Depuis quelques années, le monitorage de l’anesthésie pédiatrique devient déplus en plus complexe et tout particulièrement en anesthésie cardiaque. L’objectif de ce travail consiste à passer en revue la littérature actuelle qui traite du monitorage usuel et spécialisé. Le monitorage usuel peut être influencé par les modifications de la fréquence cardiaque, du courant sanguin, du débit cardiaque et de l’oxygénation provoqués par les anomalies cardiaques congénitales, du type de chirurgie et des retentissements de la circulation extracorporelle. L’utilisation du monitorage spécialisé est de plus en plus répandu et concerne particulièrement la circulation cérébrale, l’oxygénation du sang veineux mêlé, la mesure du débit cardiaque et la coagulation. Au cours des cinq dernières années, le développement de sondes plus petites a généré de nombreuses publications sur l’échocardiographie transoesophagienne. L’utilisation des moniteurs actuels de la fonction cérébrale demeure sujet à controverse bien qu ’un moniteur de perfusion cérébrale adéquat demeure toujours aussi essentiel, confirmant ainsi le besoin de recherches supplémentaires sur ce sujet. Ce survol se portera spécialement sur les champs d’activités qui ont connu les changements les plus profonds et sur le monitorage qui établira les standards du futur. Finalement, au milieu de cette technologie, il ne faut jamais oublier que le moniteur clinique le plus important se trouve au chevet du malade en la personne du médecin.     

Use of a pulse oximeter for determination of systolic blood pressure in a helicopter air ambulance

INTRODUCTION: Traditional methods of determining blood pressure may be unreliable (auscultation or palpation) or unavailable (direct arterial cannulation) in the air medical environment. The authors investigated the combination of a pulse oximeter with a standard sphygmomanometer (blood pressure) cuff as an alternative method. METHOD: The pulse oximeter is applied to a finger on the same upper extremity on which a standard blood pressure cuff had been applied. A baseline blood pressure was obtained by palpation or an automated blood pressure device. One minute later, the systolic blood pressure (SBP) was determined by inflating the blood pressure cuff until the pulsatile display on the pulse oximeter was obliterated. This was taken as the systolic blood pressure. RESULTS: Complete data were obtained on 116 patients, with 223 data pairs. The SBP as obtained by the baseline method was strongly correlated with the SBP obtained by the pulse oximeter display obliteration method (r = 0.90, p < 0.001). CONCLUSION: The obliteration of the wave form display on a pulse oximeter is an accurate, convenient, inexpensive and readily available alternative method of determining SBP.     

A multi-institutional study of interobserver agreement in the evaluation of dementia with rCBF/SPET technetium-99m exametazime (HMPAO)

Although specific patterns of technetium-99m exametazime [^99mTc-hexamethylpropylene amine oxime (HMPAO)] brain single-photon emission tomography (SPET) uptake have been described for patients with dementia, no multi-institutional study has evaluated interobserver agreement. Interobserver agreement for ^99mTc-HMPAO brain SPET uptake patterns in 50 clinically diagnosed demented subjects from four institutions were studied. Neurologists classified these subjects as presumed Alzheimer's disease (n=21), confirmed Alzheimers's disease (n=10), multi-infarct dementia (n=9), HIV-related dementia (n=7), or mixed (n=3). In addition 20 normal (five per institution) ^99mTc-HMPAO studies were included in a randomized blinded evaluation by three readers each from a different institution. Readers classified the general appearance of the images in one of four categories: normal, globally decreased uptake, focal areas of decreased uptake, and patchy changes in uptake. Consensus results show a sensitivity of 72% and specificity of 79% for identifying abnormalities in scans of demented subjects. Readers also rated ^99mTc-HMPAO uptake in eight designated regions in each hemisphere. Significant reader agreement (P < 0.01) for the classification by general appearance and the ratings of regional uptake was obtained. This study demonstrates that interpretation of regional cerebral blood flow/SPET images is concordant across multiple institutions and readers.Subject studies performed at St. Vincent's Hospital, New York     

Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro

Decreased production of erythropoietin (Epo) as a result ofreduced renal mass is considered the main factor underlyingthe anaemia that is invariably associated with chronic renalfailure (CRF). Other mechanisms such as accumulation of inhibitorsof Epo also contribute. In this study we show that supernatantfrom peripheral blood mononuclear cells (PBMC) cultured frompatients with CRF inhibits Epo release by Hep G2 cells in vitro.Ten patients (5 male) with CRF (mean age 42 years, range 25–60)were studied. Five were approaching end-stage renal failureand five were maintained on haemodialysis (HD). Ten apparentlyhealthy volunteers were used as controls. Full blood countsand serum Epo (RIA) levels were determined and adherent PBMCwere cultured for 48 h with and without LPS. There was a significantrise in TNF- and IL1-ß levels measured in monocytesupernatant (MS) from patients and controls after LPS stimulation(P<0.05) and in IL-l levels in patients (P<0.05). IL-1ßlevels were higher in patients compared to controls both beforeand after stimulation with LPS (P<0.05). Hep G2 cells werecultured in 5% CO₂ and 20% O₂ and incubated with MS from patientsand controls for 24 h. Hep G2 harvest fluids were then analysedfor Epo levels, which were expressed as a function of totalcell protein (mU/mg). Epo production was inhibited by MS frompatients compared to controlsboth before and after stimulationwith LPS (P<0.0001). There was, however, no direct correlationbetween the degree of Epo suppression and concentrations ofMS TNF-, IL-l, and IL-ß. Inhibition byspecific polyclonalanti-TNF- antibodies and anti-IL-ß antibodies didnot abrogate the inhibition ofEpo release by Hep G2 cells. Theseresults demonstrate that although PBMC from patients with CRFproduce factors that inhibit Hep G2 cell secretion of Epo invitro, this effect does not appear to be directly related tothe proinflammatory cytokines TNF-, IL-l, and IL-ß.     

Daily variability in resting levels of cardiovascular variables in normal subjects and those with homozygous sickle cell disease

Measurements were made of cardiovascular variables and oral temperature in 16 male subjects with homozygous sickle cell disease (SS) and in 17 matched controls (AA) at 10.00 a.m., 1.00 p.m. and 4.00 p.m. All subjects were in a rested state throughout. At 10.00 a.m., mean arterial pressure was lower, while heart rate, total forearm blood flow and cutaneous red cell flux in the forearm were higher in SS than AA. Vascular resistance in total forearm and forearm skin, calculated by dividing arterial pressure by blood flow or red cell flux, were lower in SS but hand cutaneous red cell flux and vascular resistance were not significantly different in SS and AA. In both SS and AA, there were parallel increases over the three sessions, in mean arterial pressure (by 12 and 10%, respectively) forearm vascular resistance (by 17 and 27%) and hand cutaneous vascular resistance and hand cutaneous resistance (by 240 and 350%) whereas forearm blood flow and hand cutaneous red cell flux fell. By contrast, forearm cutaneous resistance showed no change during the day in SS, but increased progressively in AA (by 75%). These results indicate that, during the day, there is progressive vasoconstriction in forearm muscle and hand skin in SS and AA and also in forearm skin of AA that contributes to a progressive rise in the resting level of mean arterial pressure. We suggest this daily variability should be considered in studies of cardiovascular function: within a given study they should be performed at the same time of day.     

The effects of single oral doses of 17β-oestradiol and progesterone on finger skin circulation in healthy women and in women with primary Raynaud's phenomenon

The effects of sex, the menstrual cycle, oral contraceptives, pregnancy, and the menopause on skin perfusion in healthy women and in patients with Raynaud's phenomenon suggest a role of female sex hormones. However, no clear relation between skin blood flow and circulating concentrations of oestrogens or progestogens has yet been found. The aim of this study was to investigate the effect of orally administered 17-oestradiol and progesterone on finger skin blood flow before and during heat and cold challenge in 17 healthy normotensive women and in 12 women with Raynaud's phenomenon.In each subject standardized finger heating (45°;C water bath, 10 min) and cooling tests (15°;C water bath, 5 min and 20 min recovery) were performed twice on the second (or third) day of two consecutive menstrual cycles. 17-Oestradiol (9 mg) or progesterone (300 mg) were given before the second test, after a first test with placebo. Both hormonal doses resulted in (high) physiological concentrations. Fingertip skin temperature and laser Doppler flux were measured.There were no significant differences in the test results after placebo and after progesterone. Although values of fingertip skin temperature and laser Doppler flux after 17-oestradiol tended to be higher only the precooling values in the healthy subjects reached significance: fingertip skin temperature respectively with placebo and with oestradiol (mean (SD)): 32.7 (1.0) and 33.1 (0.8)°;C; laser Doppler flux with placebo and with oestradiol: 33.6 (11.7) and 42.2 (9.5) perfusion units; both P<0.05). In this study, single oral doses of female sex hormones had only minor effects on finger skin circulation, both in control subjects and in women with Raynaud's phenomenon.     

Surface Modification of Poly(lactide-co-glycolide) Nanospheres by Biodegradable Poly(lactide)-Poly(ethylene glycol) Copolymers

The modification of surface properties of biodegradable poly(lactide-co-glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethlene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da, respectively) were studied. The results reveal the formation of a PLA: PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems. A similar biodistribution pattern of PLA:PEG 3:4 to PEG 2:5 coated particles may indicate that poly(ethylene glycol) chains in the range of 2000 to 5000 can produce a comparable effect on in vivo behaviour.     

Blood flow and metabolic microenvironment of brain tumors

Conclusions Summarizing thesein vivo data in the context of brain tumor therapy, the following aspects are of particular importance: Low and heterogeneous tumor blood flow may — in addition to the limiting effects of the blood-brain barrier — result in compromised delivery of drugs from blood to the tissue. Low tumor pO₂ reduces sensitivity to standard radiation and O₂-dependent anticancer drugs. Treatment efficacy may be further altered by changes of tumor pH. Particularly acidosis can decrease radiation sensitivity and modulate the cytotoxicity of anticancer drugs. In the following presentations, these aspects will be discussed regardingin vivo data obtained with positron emission tomography.     

Evaluation of regional haemodynamics and alterations of vascular wall of the lower limbs in hypertensive subjects

This study was designed to analyse the relationship betweenarterial hypertension and changes in arterial blood flow andvascular wall damage of the lower limbs in hypertensive patientswith various degrees of hypertension. Six hundred and fifty-four hypertensive patients (421 malesand 233 females) aged 35 to 70 years and 88 healthy subjects(63 males and 25 females) aged 39 to 60 years were studied.Strain-gauge plethysmography of the lower limbs was used tocalculate arterial calf blood flow (RF), arterial calf bloodflow after post-ischaemic hyperaemia (PF), basal and minimalvascular resistances (BVR and MVR), time to reach peak flow(tPF), time until 50% reduction of peak flow (tT) and totalrecovery time (tT). In 108 (67 males and 41 females) of the hypertensive patients,a morphological study by echo-Doppler duplex scanning of thepopliteal artery was performed to measure medial-intimal thickeningand popliteal lumen diameter. Our results indicate that regional haemodynamics of the lowerlimbs worsened in hypertensives in comparison with control subjects.In addition, the change in peripheral haemodynamics was relatedto the degree of hypertension. Moreover, medial-intimal thickeningwas significantly (P<0.05) higher in severe hypertensivesthan mild hypertensives. Popliteal lumen diameter was significantly(P<0.05) lower in severe hypertensives than moderate andmild hypertensives. In all these subjects mean blood pressurewas correlated directly (r=0.31; P<0.001) with medial-intimalthickening and inversely (r= – 0.37; P<0.001) withpopliteal lumen diameter. Multiple regression analysis indicatedthat mean blood pressure, age and serum cholesterol were independentlycorrelated to medial-intimal thickening. This relationship wasnot influenced by the diabetic patients and smokers among thegroups. Our results indicate that hypertension impairs peripheral flowand encourages the development of medial-intimal thickening.     

Tumor-associated lymphocytes (TAL) are competent to produce higher levels of cytokines in neoplastic pleural and peritoneal effusions than those found in sera and are able to release into culture higher levels of IL-2 and IL-6 than those released by PBMC

This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1, 2 and 6, tumor necrosis factor- (TNF) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3⁺ and CD8⁺ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16⁺ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16⁺ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions. The CD39 antigen was higher on TAL from peritoneal effusions than on PBMC of the same patients. The levels of IL-1 and sIL-2R in peritoneal effusions did not differ from those measured in the sera of the same patients, while the levels of IL-2, IL-6, and TNF were higher in the peritoneal effusions. The levels of IL-2, IL-6, TNF, and sIL-2R, but not IL-1, in pleural effusions were significantly higher than those found in the sera of the same patients. The amounts of IL-2 and IL-6 produced by TAL were generally higher than those released by PBMC. The secretion of cytokines IL-1, IL-2, and sIL2R by PHA-stimulated PBMC was lower, but IL-1 and IL-6 secretion was higher in cancer patients with neoplastic effusions than in either cancer patients without neoplastic effusions or normal subjects. The CD25 expression on PHA-stimulated PBMC derived from cancer patients with neoplastic effusions was in the same range as that of cancer patients without neoplastic effusions and normal subjects. These findings suggest that TAL may be able to produce cytokines and may be amenable to immune manipulation.Abbreviations FITC Fluorescein-isothiocyanate - IL Interleukin - mAb Monoclonal antibody - MHC Major histocompatibility complex - NK Natural killer - PBMC Peripheral blood mononuclear cells - PHA Phytohemagglutinin - TAL Tumor-associated lymphocytes - TIL Tumor-infiltrating lymphocytes - TNF Tumor necrosis factor- - sIL-2R Soluble interleukin-2 receptor