Comparing the haemodynamic effects of high- and low-dose opioid anaesthesia: a secondary analysis of a randomised controlled trial.

Post-induction hypotension (MAP < 65 mmHg) occurs frequently and is usually caused by the cardiovascular adverse effects of the anaesthetic induction drugs used. We hypothesize that a clinically significant difference in the incidence and severity of hypotension will be found when different doses of propofol and remifentanil are used for induction of anaesthesia. METHODS: This is a secondary analysis of a randomised controlled trial wherein four groups (A-D) of patients received one out of four different combinations of propofol and remifentanil, titrated to a predicted equipotency in probability of tolerance to laryngoscopy (PTOL) according to the Bouillon interaction model. In group A, a high dose of propofol and a low dose of remifentanil was administered, and across the groups this ratio was gradually changed until it was reversed in group D. Mean and systolic arterial blood pressure (MAP, SAP) were compared at four time points (Tbaseline, Tpost-bolus, T3min, Tnadir) within and between groups Heart rate, bispectral index (BIS) and the incidence of hypotension were compared. RESULTS: Data from 76 patients was used. At Tpost-bolus a statistically significant lower MAP and SAP was found in group A versus D (p = 0.011 and p = 0.002). A significant higher heart rate was found at T3min and Tnadir between groups A and B when compared to groups C and D (p = < 0.001 and p = 0.002). A significant difference in BIS value was found over all groups at T3min and Tnadir (both p < 0.001). All other outcomes did not differ significantly between groups. CONCLUSION: Induction of anaesthesia with different predicted equipotent combinations of propofol and remifentanil did result in statistically different but clinically irrelevant differences in haemodynamic endpoints during induction of anaesthesia. Our study could not identify preferable drug combinations that decrease the risk for hypotension after induction, although they all yield a similar predicted PTOL.

Comparison of haemodynamic- and electroencephalographic-monitored effects evoked by four combinations of effect-site concentrations of propofol and remifentanil, yielding a predicted tolerance to laryngoscopy of 90.

This prospective study evaluates haemodynamic and electroencephalographic effects observed when administering four combinations of effect-site concentrations of propofol (CePROP) and remifentanil (CeREMI), all yielding a single predicted probability of tolerance of laryngoscopy of 90% (PTOL = 90%) according to the Bouillon interaction model. We aimed to identify combinations of CePROP and CeREMI along a single isobole of PTOL that result in favourable hypnotic and haemodynamic conditions. This knowledge could be of advantage in the development of drug advisory monitoring technology. 80 patients (18-90 years of age, ASA I-III) were randomized into four groups and titrated towards CePROP (Schnider model, ug⋅ml-1) and CeREMI (Minto model, ng⋅ml-1) of respectively 8.6 and 1, 5.9 and 2, 3.6 and 4 and 2.0 and 8. After eleven minutes of equilibration, baseline measurements of haemodynamic endpoints and bispectral index were compared with three minutes of responsiveness measurements after laryngoscopy. Before laryngoscopy, bispectral index differed significantly (p < 0.0001) between groups in concordance with CePROP. Heart rate decreased with increasing CeREMI (p = 0.001). The haemodynamic and arousal responses evoked by laryngoscopy were not significantly different between groups, but CePROP = 3.6 µg⋅ml-1 and CeREMI = 4 ng⋅ml-1 evoked the lowest median value for ∆HR and ∆SAP after laryngoscopy. This study provides clinical insight on the haemodynamic and hypnotic consequences, when a model based predicted PTOL is used as a target for combined effect-site controlled target- controlled infusion of propofol and remifentanil. Heart rate and bispectral index were significantly different between groups despite a theoretical equipotency for PTOL, suggesting that each component of the anaesthetic state (immobility, analgesia, and hypnotic drug effect) should be considered as independent neurophysiological and pharmacological phenomena. However, claims of (in)accuracy of the predicted PTOL must be considered preliminary because larger numbers of observations are required for that goal.

Influence of Bayesian optimization on the performance of propofol target-controlled infusion.

BACKGROUND: Target controlled infusion (TCI) systems use population-based pharmacokinetic (PK) models that do not take into account inter-individual residual variation. This study compares the bias and inaccuracy of a population-based vs a personalized TCI propofol titration using Bayesian adaptation. Haemodynamic and hypnotic stability, and the prediction probability of alternative PK models, was studied. METHODS: A double-blinded, prospective randomized controlled trial of 120 subjects undergoing cardiac surgery was conducted. Blood samples were obtained at 10, 35, 50, 65, 75 and 120 min and analysed using a point-of-care propofol blood analyser. Bayesian adaptation of the PK model was applied at 60 min in the intervention group. Median (Absolute) Performance Error (Md(A)PE) was used to evaluate the difference between bias and inaccuracy of the models. Haemodynamic (mean arterial pressure [MAP], heart rate) and hypnotic (bispectral index [BIS]) stability was studied. The predictive performance of four alternative propofol PK models was studied. RESULTS: MdPE and MdAPE did not differ between groups during the pre-adjustment period (control group: 6.3% and 16%; intervention group: 5.4% and 18%). MdPE differed in the post-adjustment period (12% vs. -0.3%), but MdAPE did not (18% vs. 15%). No difference in heart rate, MAP or BIS was found. Compared with the other models, the Eleveld propofol PK model (patients) showed the best prediction performance. CONCLUSIONS: When an accurate population-based PK model was used for propofol TCI, Bayesian adaption of the model improved bias but not precision. CLINICAL TRIAL REGISTRATION: Dutch Trial Registry NTR4518.

Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration.

This review describes the basics of pharmacokinetic and pharmacodynamic drug interactions and methodological points of particular interest when designing drug interaction studies. It also provides an overview of the available literature concerning interactions, with emphasis on graphic representation of interactions using isoboles and response surface models. It gives examples on how to transform this knowledge into clinically and educationally applicable (bedside) tools.

Transplacental transport of IgG antibodies to preterm infants: a review of the literature.

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections. Therefore, the newborn is dependent on transplacental transport of Immunoglobulin G (IgG), an active, FcRn receptor mediated process. Fetal IgG rises from approximately 10% of the maternal concentration at 17-22weeks of gestation to 50% at 28-32weeks of gestation. If transplacental acquired IgG is lower in preterm than in term infants, preterm infants are especially at risk for these vaccine-preventable diseases. The aim of this study was to review the transplacental transfer of IgG against vaccine-preventable diseases (measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, tetanus, pertussis and polio) to (pre)term infants and to identify factors that influence the transplacental transfer of these antigens. After selection, 18 studies on transplacental transport to preterm infants were included. In general, these studies showed for all antibodies that preterm infants have lower antibody concentrations compared with term infants. Maternal and infants antibody concentrations showed a strong correlation in 7 of the included studies. Infant antibody concentration was not associated with parity, maternal age, height or weight. Infants of vaccinated mothers had lower anti-measles antibody titers than infants of natural immunized mothers. IgG titers of preterm infants decrease earlier in life below protective antibody titers than term infants. Combined with their immature immune system, this puts preterm infants at increased risk for vaccine-preventable diseases.

Multidisciplinary ALS care improves quality of life in patients with ALS.

OBJECTIVE: To examine the effect of multidisciplinary ALS care on the quality-of-life (QoL) in patients with ALS and their caregivers. METHODS: In a cross-sectional study, 208 patients with ALS and their caregivers were interviewed. QoL was assessed using the 36-item Short Form Health Survey (SF-36) and two visual analogue scales (VAS). Criteria for multidisciplinary ALS care were: an ALS team headed by a consultant in rehabilitation medicine and consisting of at least a physical therapist, occupational therapist, speech pathologist, dietician and a social worker; use of the Dutch ALS consensus guidelines for ALS care; and at least six incident ALS patients per year. RESULTS: Clinical characteristics and functional loss of the 133 patients receiving multidisciplinary ALS care and the 75 patients receiving general ALS care were similar. The percentage of patients with adequate aids and appliances was higher in those with multidisciplinary ALS care (93.1 vs 81.3%, p = 0.008), whereas the number of visits to professional caregivers was similar in both groups. Patients in the multidisciplinary ALS care group had a better mental QoL on the SF-36 Mental Summary Score than those in the general care group (p = 0.01). The difference in QoL was most pronounced in the domains of Social Functioning and Mental Health, and was independent of the presence of aids and appliances. No significant differences were found in the SF-36 Physical Summary Score, VAS, or in QoL of caregivers of patients with ALS. CONCLUSION: High standard of care improves mental quality-of-life in patients with ALS.

[The symptomatic treatment of amyotrophic lateral sclerosis]. / De symptomatische behandeling van amyotrofische laterale sclerose.

Patients with amyotrophic lateral sclerosis (ALS) have symptoms of progressive muscle weakness, of disturbed speech and swallowing, and in the terminal phase those of respiratory weakness. Treatment options, in particular those for excessive weight loss and respiratory weakness, should be introduced to the patients and their families when the patient is emotionally capable and before dysarthria severely hampers communication. Special equipment for keeping the patient as mobile as possible should be made available much earlier than in the case of other diseases of the muscles as in ALS progression is much faster. Cramps, pathological crying or laughter, spasms, and spasticity can all be treated by medication. When speech can no longer be understood, adaptive strategies such as sign language, mime, posture and communication apparatus varying from a note pad to advanced computer systems can be used. Sialorrhoea, caused by difficulty swallowing with its accompanying danger of aspiration can be halted by the use of medication, by radiotherapy and by the injection into the salivary glands of botulin A toxin. Weight loss, also a result of dysphagia, can be avoided by eating frequent small meals or if necessary performing a percutaneous endoscopic or radiological gastroscopy. Excess mucus in the respiratory tract can be treated with anticholinergics. Difficulty in coughing up thick and sticky mucus cannot always be adequately helped. Respiratory weakness is treatable by external respiratory supportive therapy using a nasal mask, as well as invasive respiratory support via a trachcostoma and by treating the symptoms of respiratory weakness. The latter form of treatment is palliative and forms part of terminal care. During the terminal phase restlessness, anxiety, pain, and dyspnoea require the most attention. Treatment requires careful multidisciplinary cooperation.

Development and implementation of the Dutch protocol for rehabilitative management in amyotrophic lateral sclerosis.

INTRODUCTION: In the Netherlands, rehabilitation care plays an important role in the symptomatic and palliative treatment of ALS patients. However, until 1999 there were no guidelines or practice parameters available for the management of ALS. Therefore, the Dutch protocol for rehabilitative management in ALS was developed. We describe the development process, the outcome and implementation of the protocol. METHODS: A concept management protocol was written and the Delphi method was selected to develop the protocol further. This method comprises repetitive discussion sessions from postulates, using a combination of written questionnaires and work-conferences. Between 80 and 90 persons (rehabilitation team members of different professional backgrounds and neurologists) were involved in this process. The protocol was implemented by sending it to all consultants in rehabilitation medicine in the Netherlands; they were asked to inform all the treatment team members about the final protocol and to implement it in their treatment of ALS patients. RESULTS: The protocol was developed in 1999, implemented in 2000 and evaluated in 2001. Recommendations for improvement were made during the evaluation and improvements are currently being developed by an expert group. The protocol is widely used (88.9%) by consultants in rehabilitation medicine and their treatment teams in the Netherlands. CONCLUSIONS: The Dutch protocol for rehabilitative management was developed to provide an optimal and adequate care plan for patients with ALS. It is widely used in the Netherlands.

Primary liver cancer in two sisters in Holland with intermittent acute porphyria.

Two sisters living in Holland, with a niece now living in South Africa, were reported in 1958 to have inherited intermittent acute porphyria (IAP). In 1994 both sisters died from primary liver cancer. Other reports have also noted an increased mortality from carcinoma of the liver in porphyrics. Porphyria variegata has a high prevalence in white and coloured South Africans, and it would be relatively easy to ascertain whether those who have inherited the gene for this disorder, in South Africa, have a higher than reported mortality from liver cancer. If they do, consideration should be given to ways to reduce their risk of developing and dying from this cancer.

The Standomobile: a new, electrically powered, mobile stand up device for use in paraplegia. Case report.

In this case study a specially designed electrically powered mobile stand up device, for a patient with a complete spinal cord lesion under cervical level C7, is described. It has proved to be satisfactory in a flower nursery, where both sitting and standing work is done. It is a usable aid to help patients to return to their work environment.

Explanation procedure with special emphasis on the ITI implant system.

Removal of implants is performed in cases of irreversible implant failure and in patients having psychological problems with implants. The explantation procedure can be complicated in some situations. In the present article, techniques of explantation and some related considerations are presented.

Inter-rater and intra-rater reliability of disability ratings based on the modified D Code of the ICIDH.

Since application of the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) in its full form proved to be impractical, the use of selected parts, or of instruments based on the ICIDH, has been suggested. We have assessed the inter- and intra-rater reliability of disability ratings using a screening instrument, based on the D Code of the ICIDH. The level of functional abilities of all new patients (n = 39) seen by a resident at our outpatient clinic in an 11-week period was rated on a four-point scale for each of 28 items in five ability categories. Independent ratings were done by a resident and his supervisor (inter-rater reliability). Repeated rating by the resident was used to assess intra-rater reliability. Calculation of the inter- and intra-rater reliability was based both on the method of the relative agreement and on the measure kappa. The results showed relative agreements of greater than or equal to 82%, and kappa values of greater than or equal to 0.71 were found. This study shows that in a teaching hospital very satisfactory inter-rater and intra-rater reliabilities using a short instrument based on the D Code of the ICIDH can be achieved. It can therefore be recommended as a method for global disability rating.