Once versus individualized multiple daily dosing of aminoglycosides in critically ill patients

The purpose of this study was to evaluate the once daily dosing [ODD] program in critically ill Egyptian patients compared to individualized multiple daily dosing [MDD] in terms of clinical and bacteriological efficacy. In addition, the incidence of nephrotoxicity associated with both regimens in this specific group of patients was assessed. Fifty-two patients with suspected or confirmed bacterial infections admitted to the Critical Care Medicine Department, Kasr El-Aini-Cairo University Hospitals comprised the study population. The amikacin group [30 patients] was sub-divided into 14 patients receiving amikacin ODD [1 g i.v.] and 16 patients receiving amikacin in MDD [500 mg i.v./dose]. The gentamicin group [22 patients] was sub-divided into 10 patients receiving the drug ODD [240 mg i.v.] and 12 patients receiving gentamicin MDD [80 mg i.v./dose]. Amikacin or gentamicin serum levels were determined by the enzyme multiplied immunoassay technique using Emit 2000. MDD regimen was adjusted based on the individual pharmacokinetic parameters using the Sawchuk-Zaske method. There was no significant difference between the two dosing regimens with regard to clinical and antibacterial efficacy or incidence of nephrotoxicity of both gentamicin and amikacin groups. In the ODD regimen, duration of treatment had no effect on increasing incidence of nephrotoxicity unlike the individualized MDD regimen. No dose adjustments were needed in the once daily dosing regimen since trough concentrations have never been above toxic level. The study showed that the ODD regimen is preferred in critically ill patients to individualized MDD as shown by comparable efficacy, nephrotoxicity and lesser need for therapeutic drug monitoring and frequent dose adjustments required in the individualized MDD regimen

Pulmonary veins potential recording in paroxysmal, persistent atrial fibrillation: prevalence and technical aspects

The focal theory of atrial fibrillation [AF] has tempted the electrophysiologists to try radically curing AF via radiofrequency [RF] ablation. Interventional ablation depended on localizing and precisely recording pulmonary vein potentials [PVPs] from the origins of the 4 pulmonary veins [PVs] and less commonly from the ostia of the superior vena cava [SVC], and coronary sinus [CS]. The present study is intended to assess the prevalence and feasibility of recording PVPs in patients [pts] with paroxysmal and persistent AF. The study included 27 pts, [14M, 13F] of variable age groups [27-62 yrs], mean age 39.3 +/- 10 and highlysymptomatic paroxysmal and/or persistent AF. refractory to more than two antianhythmic drugs. all had normal thyroid functions. All pts were subjected to left atrial mapping after a trans-septal puncture and introduction of 2 catheters, one via an 8F femoral sheeth [the Lasso catheter] a special circumferential pulmonary vein catheter for recording, and the other was the ablation catheter. Pulmonary venography preceded the PV-mapping to localize the site and to delineate the size of PV and hence the diameter of the lasso catheter that will be used. A coronary sinus hexapolar catheter was placed distally in the coronary sinus. PV potentials were mapped in both sinus rhythm [for Rt. PVs] and with distal coronary sinus or left atrial appendicular [LAA] pacing [for left PVs]. An arrhythmogenic PV was defined on the basis of documented ectopy [single or multiple] with or without conduction to the LA. PV potentials can be described as sharp electrical activity superimposed on atrial activity, that can be separated by LAA pacing in the Left sided veins. or recorded without pacing from Rt sided veins. One hundred and four out of 108 PVs were mapped. Pulmonary venous potentials could be recorded in 25 out of 27 left superior PVs [92.6%], 21 out of 26 left inferior PV [80.8%], 20 out of 25-" right superior PVs [80%] and in 19 out of 26 right inferior PVs [73%]. Pts were arbitrarily divided according to age into 2 age groups; 14 below 40 and 13 above the age 40y. Compared to the younger age oup, those above 40 yrs. exhibited significant lower prevalence of PVP [3.6 +/- 0.6 Vs 2.6 +/- 1.3 respectively]. proximal CS and the former was superceded by pacing from LAA. PVPs cou1dnt be recorded in 2 out of 27 LSPVs, 5 out of 26 LIPVs, 5 out of 25 RSPVs. 7 out of 26 RIPVs, Four PVs were not mapped due to technical problems. Three cases were complicated with cardiac tamponade the first due to puncture of the LA appendage with the transieptal needle, the case due to extensive ablation and the 3 due to over anticoagulation. Two ps [7.4%] developed mild pericardial effusion that was asymptomatic and disappeared during follow-up and one developed TIA. No mortality was recorded. Pulmonary vein potential recording is an essential prerequiste for successful RE ablation of focal AF using Lasso technique. Our data point to the feasibility anti safety of recording in non rheumatic cases and stress the importance of the learning curve. Left superior, Left inferior, Rt superior, Rt inferior pulmonary veins in that order of frequency are arrhytbmogenic foci generating PV potentials. Left sided and superior PVs are more frequently a source of PVPs representing triggers that initiate AF than right sided and inferior PVs. The prevalence of PVPs recording progressively declines with aging possibly pointing to the increasing role of micro reentry in the genesis of AF and the diminishing of PV triggers. Identification of PVPs is highly important and could be easily detected without pacing in case of Rt sided PVs and with CS or LAA pacing for left sided PVs. Pacing from distal CS was noted to promote better separation of PVPs from the atrial activity than pacing from proximal CS and the former was superceded by pacing from LAA

Quality indicators in our ICU, a tool for improvement!

Patients included in the study were 96 consecutive eligible patients admitted to mixed medical/ surgical ICUs between January, 2008 and March, 2008. Our objective was to use a consensus process to develop a preliminary set of quality measures to assess care in our ICU. We built on earlier efforts of the Spanish Society of Intensive Critical Care and Coronary Units [SEMICYUC], in May 2005 to propose specific measures of the structure and process of ICU care. We used an informal iterative consensus process to identify and refine a set of candidate quality measures. Retrospective cohort study. Department of critical care medicine, Cairo university hospitals. A total of 96 patients admitted to our ICU from January 2008 to March 2008. Intervention: None. This study was conducted to detect the implementation of a set of indicators that measure the quality of care in intensive care units [ICU] in Cairo university hospitals. The study was done for 3 months in 2 ICUs. All patients were studied for the implementation of the fundamental quality indicators [QI] that was previously published by the Spanish Society of Intensive and Critical Care and Coronary Units [SEMICYUC]. Our results showed that standards [6, 14 and 17] were not applicable our ICU. Implementation of indicators 7, 15 and 18 were poorly applied in our ICU. Poor performance was defined as a score of less than 50% of the standard. On the other hand, all other indicators were implemented with different scores in our ICU. As quality assurance become an important issue in modern ICU practice, ICU quality indicators has become a useful tool to measure ICU quality performance. Our ICU is still lacking implementing quality practice, we need intensive efforts to spread the culture of continuous quality improvement in our ICUs

Pharmacogenetics oriented therapeutic drug monitoring of digoxin in critically ill patients

This study was performed to outline the different MDR-1 [Multi-Drug Resistance-1] genotypes in a sample of 37 Egyptian patients suffering from atrial fibrillation [AF] and/or congestive heart failure [CHF] and are using digoxin, to assess the role of MDR-1 genotypes polymorphism in affecting steady state serum digoxin therapeutic levels, and studying the consequences on patients' clinical outcome. Two venous blood samples were drawn from each patient; the 1[st] sample was taken, on admission, for DNA extraction and genotyping and the 2 [nd] was taken, 6 hours post dose after reaching steady state concentration, for serum digoxin assay. Serum digoxin. levels were assayed using EMIT 2000 analyzer, and MDR-1 genotyping was done using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] technique. Twenty patients [54.1%] showed serum digoxin levels within the therapeutic range, 12 patients [32.4%] showed serum digoxin levels under the minimum effective concentration [p< 0.9 ng/ml], while 5 patients [13.5%] showed serum digoxin levels over maximum safety concentration [> 2 ng/ml], with P value of 0.0001 among the three groups. MDR-1 genotyping revealed ten patients [27%] carrying the homozygous mutant TT genotype, 27 patients [73%] carrying the heterozygous mutant CT genotype, with no patient showing the wild CC genotype. Allelic distribution showed 42% for the wild type C allele while 58% for the homozygous mutant T allele. Patients carrying the homozygous mutant TT genotype showed significantly lower serum digoxin levels compared with those carrying the heterozygous mutant CT genotype [P value: 0.009]. Patients with significant improvement carried the CT genotype and had serum digoxin levels within the therapeutic range. In conclusion, patients with different MDR-1 genotypes had variations in their serum digoxin levels and identification of MDR-1 variations was found useful in predicting therapy outcome. We recommend further extensive work on large samples to study the important role of MDR-1 gene in affecting the disposition of different substrates, to be able for individualizing them according to the patients' genetic profile in order to improve drug therapy and reduce inter-patient variability

Aortic root distensibility in patients with coronary artery disease

An important determinant of myocardial performance, namely cardiac afterload is largely dependent upon aortic root distensibility [AD], peripheral arterial resistance and end systolic wall stress. The latter can be reliably measured by using m-mode and 2-D echo whereas AD used to be a neglected parameter. In patients with ischaemic heart disease, the question always arises whether AD could in a way or another predict coronary arterial pathology /= 200 and /or LDL >130mg/dl in 21pts and HTN in 17pts. Following clinical evaluation including 12 lead ECG, m-mode and 2-D echocardiography, all pts underwent diagnostic CA and were subjected to transoesophageal echocardiography [TEE] using phased array multiplane 32 elements transducer [5MHz] mounted on the tip of 100cm gastroscope with Acuson Sequoia C256 system. Transoesophageal [TEE] was done while the pts in the left lateral position. The studies were recorded on videotapes for off-lines analysis. Images of the aortic root were obtained in an angle of about 120 degrees. Aortic root was measured in systole [maximal diameter] and diastole [electrocardiographic Q-wave] 3cm from cusps insertion using the trailing edge-to-leading edge method. Measurements were taken in 3 cycles and the mean value was taken, with the difference in diameter delta d as a measurement of aortic root excursion, delta p as the pulse pressure, and d=diastolic aortic root diameter. AD was expressed as =2xdelta d / delta pxd. According to CA, pts were divided into those with diseased coronary arteries 74.4% and those with a normal CA 25.6%. Compared to the normal CA group, AD was insignificantly different from that into pts with diseased CA 23.9 vs 21.4, p value = 0.573. Patients were then stratified into two groups with an age of 50yrs, SBP of 130mmHg, DBF of 80mmHg, serum cholesterol >200 and /or LDL >/= 130mg/dl and presence of DM serving as arbitrary dividing limits

Parental magnesium sulfate [MgSO4] in the treatment of atrial fibrilation [AF]

The antiarrhythmic effects of magnesium sulfate were known long ago particularly in ventricular tachycardia and in torsade de points. This study reported the results of IV MgS04 in 30 patients with chronic AF. A prospective study conducted on 30 patients [12 males and 18 females with a mean age of 54 +/- 8.12] was carried out. Underlying heart disease comprised RHD in 9 patients, CAD in 5 patients and cardiomyopathy in 2 patients. The remaining patients had no structural heart disease. Following clinical evaluation, all patients had an infusion of MgS04 at a rate of 25mg/Kg following a bolus of 35-mg/Kg-body weight. The results revealed that of the 30 patients subjected to IV MgS04 infusion, 8 were successfully cardioverted to sinus rhythm over a mean period of 2 hours [ranging from 6-12 hours], while 10 patients had achieved rate control from a mean of 140/min to 100/min. over a period of 3 hours and twelve patients failed to respond. The study concluded that IV MgSO4 can be used successfully in the therapeutic cardioversion and/or rate control of AF particularly in patients with small left atrium

Respiratory mechanics and arterial blood gases in relation to survival

This study was performed on 37 patients presenting with acute respiratory failure, who were classified as 26 COPD patients with a mean age of 60.3 [range 31-76 years] and 11 patients with restrictive lung disease with a mean age of 42.2 [range 18-72 years]. Airway pressure [peak, plateau and mean airway pressures], lung mechanics and arterial blood gases were measured and compared in survivors [29 patients] and non-survivors [8 patients] as regards the initial measurements taken immediately after mechanical ventilation, final measurements and the pattern of changes throughout the course of mechanical ventilation. Comparing both groups, data showed that in the initial measurements, there was a highly significant difference in static compliance [cstat] and airway pressures [peak, plateau and mean airway pressure], but an insignificant difference was found in airway resistance, AutoPEEP, work rate and ABG. While, in the final measurements, with an improvement of the lung mechanics in survivors, there was a significant difference between the two groups in all the above-mentioned measurements, except ABG which still showed an insignificant difference

Hemodynamic effects of different modes of positive pressure mechanical ventilation

Many patients admitted to the ICU are in need for mechanical ventilation. Ventilators directly affect cardiovascular performance by changing either lung volume or intrathoracic pressure. As oxygen delivery to various organs is the product of regional blood flow and oxygen content, the effect of different modes of positive pressure ventilation on circulatory dynamics and oxygen transport are to be compared. From the results obtained it was concluded that positive pressure ventilation had adverse effects on circulatory dynamics. Choosing the optimal ventilatory mode as well as the best weaning policy should be guided by the underlying clinical state and followed up hemodynamically by noninvasive, and if necessary, invasive means

Drug selection in ventricular tachycardia electrophysiologic VS. holter approach

Twenty one patients with symptomatic sustained ventricular tachycardia [VT] all males [with mean age of 55 years], and largely with prior myocardial infarction [93%] underwent serial electrophysiologic drug testing. All patients had at least one electrocardiographically documented attack of V.T. All patients were subjected to a complete control EPS. Reproducible induction of VT was the rule in all patients having documented sustained VT, but in none of a control group of 10 patients with similar ischemic heart disease but with no documented V.T. Inducible sustained VT could be ultimately prevented in 16 pts. [76%] [gpA] after a mean of 3 +/- 3 tests. During a mean follow-up of 16 +/- 36 months 15 patients in gp A [93.7%] had no recurrence of VT. On the other hand of the 5 pts discharged on drug which did not prevent sustained VT induction [gp.B], only one had recurrence of VT [20%]. Holter monitoring revealed persistence of malignant ventricular arrhythmia [couplets. triplets and multifocal VPB] in 6 pts. in gp A. However, only 1/16 had recurrence [16%]. Serial EP testing had high predictive value for long term efficacy of antiarrhythmic drug therapy [93.7%] but low predictive value for recurrence [20%]. Thus, inefficacy as shown by inducibility of sustained VT or positive holter recording of malignant ventricular arrhythmias did not preclude a good clinical outcome. For successful therapy of life -threatening VT particularly in the selling of ischemic heart disease and post-myocardial infarction phase, rational rather than empiric pharmacologic drug selection is highly justified. PES was shown by our study to be an effective method to guide drug selection

Follow-up of implanted pacemakers: invasive versus non-invasive testing

This study is the first detailed report of permanent pacing in 120 pts. Carried out in Cairo University hospitals through the experience of the critical care center over the past five years. During the latter period, 120 permanent PM belonging to various manufactures were permanently implanted. Implantation was endocardial in 114 pts. Via the subclavian puncture carried out by the cardiologist, and epicardial [6 pts.] conducted by a cardiac surgeon. PM implanted were of the simple VVi type in 110 pts. multiprogrammable in 10. This study showed that the overall number of implanted PM [120 over five years] is still far below the number of implantations in other centers. However, the increasing yearly distribution reflects the increasing referral of pts. And the increasing availability of PM. The routine use of EPS served to exclude loose indications for implantation and might be behind the relatively low number of pts. with PM. The study also showed that symptomatic bradyarrhythmia due to various types of AV block was the prime indication for pacing in our group of pts. Out of 120 pts. Subjected to PM implantation, 92 were followed-up in our PM clinic at an average period of 26 months. Methods of assessment included resting and dynamic ECG, magnet testing, electronic testing, chest wall stimulation, fluoroscopy, beside careful thorough clinical examination. Our system of follow-up seemed to be adequate concerning the early detection of different PM system abnormalities, and showed that non-invasive route remains mandatory to identify the underlying etiology. The latter was carried out at the time of reoperation, exposure and use of pacing system analyzer

Follow up of implanted pacemakers generator versus lead malfunction

The incidence of PM problems whether due to generator or lead malfunctions varied widely and was related to the generator and electrode characteristics, underlying cardiovascular disorder and the experience of the implanting physician. The time factor had also an important role, in so far as lead problems tend to occur during the early post-implantation period and battery depletion shows itself later on. In the group included in our study, pacemaker problems due to lead defects were 3-4 times more frequent than those due to generator depletion. Twelve pacemaker problems were encountered in 22 patients and were divided into three generator problems in six patients, four lead problems in seven patients. Two patients suffered pacemaker side effects and the remaining two had pseudomalfunctions. Generator problems included power source depletion. Oversensing, and altered programmabilty. Lead problems encountered were lead mal- position, wire break, insulation defect, and set screw unfitness. While problems related to the myocardium included exit block and undersensing of small ORS complexes. Correction of PM problems could be conducted in the majority of cases either through reprogramming of programmable PM, or reexposure in cases of generator problems or lead malposition. The above mentioned study illustrates a number of other important facts: the relatively lower rate of permanent PM implantation in comparison other centers, and the usefulness of non- invasive methods of follow-up in the majority of cases. Although follow-up is much easier and correction of malfunction is more attainable through the use of programmable PMS, it is felt that VVI PMS could still satisfy the needs both patients and physicians in our society

Verapamil in hypertension emergencies

The efficiency of verapamil HCI [isoptin] was studied in seven patients with severe hypertension. An initial IV bolus of 15 mg was injected and BP and heart rate were measured immediately, five minutes later and at fifteen minutes intervals. Verapamil infusion was then started, followed by oral verapamil for 72 hours