Comparison between intravenous boluses versus infusion of tranexamic acid [TXA] to reduce bleeding in paediatric cyanotic congenital heart disease [CHD] surgeries

Objective: To compare the intravenous boluses and intravenous continuous infusion of tranexamic acid [TXA] to reduce postoperative bleeding in cyanotic congenital heart disease surgeries

Study Design: Single-blinded randomised clinical trial

Place and Duration of Study: Anaesthesia Department, The Aga Khan University Hospital, Karachi, from July 2016 to April 2017

Methodology: Sixty patients of cyanotic congenital heart disease, undergoing either palliative or corrective surgery involving cardiopulmonary bypass [CPB], were recruited. These 60 patients were divided randomly into two groups. The infusion group received intravenous infusion of TXA at 5 mg/kg/hour while the bolus group received three intravenous boluses of 10 mg/kg after induction, after going to bypass and after protamine reversal. Data was collected through predesigned proforma. There were two primary outcomes: postoperative bleeding in the first 24 hours, and chest closure time

Results: Postoperative bleeding was 13.94 [10.27-20.18] ml/kg in the first 24 hours in infusion group and 15.05 [9.04-23.50] ml/kg in the bolus group. Chest closure time was 38.5 [25-45] in infusion group and 30 [20-46.25] minutes in the bolus group. There was no statistically significant and clinical difference between both groups regarding postoperative bleeding in the first 24 hours and chest closure time

Conclusion: These infusion and bolus groups had comparable postoperative bleeding and chest closure time

first report of a 290-bp deletion in beta-globin gene in the South of Iran

Background: beta-thalassemia is one of the most widespread disease in the world, including Iran. In this study, we reported, for the first time, A 290-bp beta-globin gene deletion in the south of Iran

Methods: Four individuals from three unrelated families with Arabic ethnic background were studied in Khuzestan Province. Red blood cell indices and hemoglobin analysis were carried out according to the standard methods. Genomic DNA was obtained from peripheral blood cells by salting out procedures. beta-globin gene amplification, multiplex ligation-dependent probe ampli?cation [MLPA] and DNA sequencing were performed

Results: The PCR followed by sequencing and MLPA test of the beta-globin gene confirmed the presence of a 290-bp deletion in the heterozygous form, along with -88C>A mutation. All the individuals had elevated hemoglobin A2 and normal fetal hemoglobin levels

Conclusions: This mutation causes beta0-thalassemia and can be highly useful for prenatal diagnosis in compound heterozygous condition with different beta-globin gene mutations

Urgent aortic valve replacement in severe aortic stenosis with severe left ventricular dysfunction and severe pulmonary hypertension: a perioperative multidisciplinary management approach

Severe aortic stenosis [AS] with reduced left ventricular systolic function and pulmonary artery hypertension [PH] is associated with poor outcome if remained untreated We report a case report of a 62 years old male patient weighing 69 kg had progressive dyspnea for 5 years and was diagnosed cardiac patient, and was scheduled for an urgent aortic valve replacement. He had severely reduced left ventricular [LV] function and severe pulmonary hypertension. The patient was put on bypass with special emphasis on myocardial protection. Tissue valve was placed and patient was successfully put off cardiopulmonary bypass on high inotrope score, which was tapered after some time. The patient was shifted to CICU after chest closure and was extubated on fast track mode. The patient was followed up for three months showing improvement in symptoms and LV function The objective of reporting the case is to highlight the role of multidisciplinary integrated approach in the perioperative period for best patient outcome

Perioperative coagulation monitoring: a new dimension

Perioperative coagulation monitoring is essential to identify surgical patients who are likely to bleed and to guide hemostatic therapy accordingly. In addition, surgery induces hypercoagulable state and its monitoring may play a role in reducing the incidence of thrombotic or thrombo- embolic events. There is a wide spread use of antiplatelet drugs by cardiologists and the monitoring and management of platelet dysfunction also becomes a vital task for anesthesiologist. Routine preoperative coagulation investigations are static tests which looked at the various parts of coagulation cascade is isolation. These tests have several limitations including reporting delays and inability to detect platelet dysfunction. Point of care testing [POC], with the use of viscoelastic testing has emerged as an alternative option for patient management during surgery. This editorial highlights the new concepts in coagulation and monitoring strategies

Early extubation in adult and pediatric open heart surgery; an experience from a tertiary care hospital of a developing country

Numerous remarkable advances have been made in the perioperative care of both adults and children undergoing cardiac surgery. Improvements in the technology of CPB, advances in the techniques of surgery, a better understanding of the pathophysiology of the postoperative period, and refinements in anesthetic and ICU care have led to changes in the perioperative management of these patients. These changes have resulted in improved outcomes and shortened hospital stay. Fast track strategy [FTS] is one of the major advances in the sub-specialty of cardiac anesthesia practice. FTS is applicable to all moderate to low risk elective open heart adult and pediatric surgeries. The role of anesthesiologist in Fast Track extubation [FTE] is very crucial and decisive as perioperative physician. Teamwork in FTE execution is very important. Every team member should respect the opinion of other team member provided the opinion is in the best interest of the patient. Multiple studies conducted as clinical audits and case series to validate the safety and feasibility of fast track extubation in adult and pediatric open heart surgical patients at our institution. Fast track extubation was practically evolved at our institution in 2007. FTE cannot be predicted in all the cases as it depends upon intra-operative and post-operative course. Safety is the priority in the decision about fast track extubation

Introduction to basic transesophageal echocardiography [TEE] and standard views

Intraoperative use of transesophageal echocardiography [TEE] for monitoring and diagnostic purposes has increased over the years in cardiac surgical patients and anaesthesiologists have taken a lead to develop expertise in performing this examination. TEE has proved to be helpful in the management of non-cardiac surgical and Intensive care unit patients particularly those patients who are haemodynamically unstable. It provides important information about ventricular and valvular anatomy and its function. Certain structures which are difficult to visualize by transthoracic echocardiography can be demonstrated easily by TEE. Several guidelines have been established for performing comprehensive TEE examination and cardiologists and anaesthesiologists follow these guidelines to identify any cardiovascular abnormality. TEE use is limited to very few centres in Pakistan, mainly due to the equipment cost and lack of expertise. In addition, there are no established TEE training institutes. The main purpose of this article is to provide basic information about transesophageal echocardiography machine, TEE probe and how to obtain standard images by probe manipulation

Exon sequencing of PKD1 gene in an Iranian patient with autosomal-dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease [ADPKD] is one of the most common genetic kidney disorders with the incidence of 1 in 1,000 births. ADPKD is genetically heterogeneous with two genes identified: PKD1 [16p13.3, 46 exons] and PKD2 [4q21, 15 exons]. Eighty five percent of the patients with ADPKD have at least one mutation in the PKD1 gene. Genetic studies have demonstrated an important allelic variability among patients, but very few data are known about the genetic variation among Iranian populations. In this study, exon direct sequencing of PKD1 was performed in a seven-year old boy with ADPKD and in his parents. The patient's father was ADPKD who was affected without any kidney dysfunction, and the patient's mother was congenitally missing one kidney. Molecular genetic testing found a mutation in all three members of this family. It was a missense mutation GTG>ATG at position 3057 in exon 25 of PKD1. On the other hand, two novel missense mutations were reported just in the 7-year-old boy: ACA>GCA found in exon 15 at codon 2241 and CAC>AAC found in exon 38 at codon 3710. For checking the pathogenicity of these mutations, exons 15, 25, and 38 of 50 unrelated normal cases were sequenced. Our findings suggested that GTG>ATG is a polymorphism with high frequency [60%] as well as ACA>GCA and CAC>AAC are polymorphisms with frequencies of 14% and 22%, respectively in the population of Southwest Iran

Promoter hypermethylation of estrogen receptor alpha gene is correlated to estrogen receptor negativity in Iranian patients with sporadic breast cancer

Breast Cancer is the most common cancer in Iranian women. Breast tumors are classified based on the estrogen receptor alpha [ER alpha] expression status into ER negative and ER positive tumors. ER negative tumors tend to have worse prognosis and less likely to respond to endocrine therapy. Aberrant methylation of gene promoter is one of the mechanisms for gene silencing in breast tumors. Because of its reversible nature, promoter methylation is a good target for new therapeutic strategies. We aimed to evaluate the frequency of this epigenetic event in ER alpha gene and its association to clinicopathological features in Iranian breast cancer patients. In this case control study the patient series consisted of 100 sporadic primary breast cancer cases [51 ER negative and 49 ER positive tumors]. None of the participants had chemo or radiotherapy before surgery. In breast tumors ER alpha promoter methylation were assessed with methylation specific polymerase chain reaction [MSP]. Data was collected on clinicopathological features of the patients. Correlation between ER alpha methylation and clinicopathological characteristics of the patients was investigated by Pearson Chi-Square and Fisher's exact test. ER alpha methylation was detected in 98% of ER negative and 65% of ER positive breast tumors. A strong correlation was found between ER alpha methylation and ER negativity in tumors [p<0.0001]. Also, ER alpha methylation has associated to progesterone receptor negativity [p<0.008] and double receptor negative status [p<0.0001] in breast tumors. ER alpha methylation occurs with high frequency in the breast tumors of Iranian breast cancer patients and may play a considerable role in pathogenesis of ER alpha negative tumors as a poor prognosis and more aggressive category. The reversible nature of DNA methylation may provide new therapeutic possibilities in ER negative breast tumors

Clinical features, DYT1 mutation screening and genotype-phenotype correlation in patients with dystonia from Iran

To test Iranian patients with primary torsion dystonia to determine the frequency of 904-906 del GAG mutation in the DYT1 [TOR1A] gene and to investigate the genotype-phenotype association for this disease. Subjects and Methods: Sixty-three patients with primary dystonia were investigated. DMA was extracted from peripheral blood and these samples were subjected to PCR-sequencing for exon 5 of the DYT1 gene. Results: Of the 63 patients, 10 [15.9%] carried the triplet GAG deletion mutation; this is a high DYT1-positive rate in comparison with other populations and the type of dystonia in this positive group was generalized in all except 1. In our patients, limbs were the most severely involved site at the time of onset and in most cases it developed to generalized form. The majority of DYT1-positive cases showed higher leg onset [5 patients, 62.5%] in comparison with higher arm onset in negative patients [20 patients, 50%]. Also, the progression to generalized dystonia in DYT1-positive patients was significantly higher than in DYT1-negative patients. The mean age at onset was 8.6 +/- 1.6 years [7-12 years] in D/H-positive patients, while mean age at onset in patients with no GAG deletion mutation was higher [15.7 +/- 11.5 years]. The DYT1 904-906 del GAG mutation is responsible for some of Iranian dystonia patients, and screening for the DYT1 deletion is significant in cases with the generalized type of primary dystonia. Also, patients with leg or arm onset at a younger age are more likely to be DYT1-positive among primary torsion dystonia Cases

Identification of alpha-globin chain variants: a report from Iran

This study was carried out to identify molecular and hematological features of alpha-globin chain variants and to evaluate their effects on the clinical and hematological characteristics in Iranian individuals suspected of having thalassemia trait. Analysis of red blood cell indices, hemoglobin [Hb] analysis and genomic DNA isolation were carried out according to standard methods. For identifying the alpha-thalassemia [alpha -thal] genotype, investigation of common Mediterranean alpha-globin gene deletions [-alpha[3.7] - alpha[4.2] - alpha[20.5] and -[MED]] was performed by Gap-FOR. To characterize chain variants the entire alpha1 and alpha2 genes that spanned from the promoter region to the poly Atail were amplified and directly sequenced. In this study, 19 members of 17 unrelated families showed alpha-chain variants. Among these cases ten alpha-chain variantsthat included Hb Setif, Hb Constant Spring [Hb CS], Hb Handsworth, Hb Icaria, Hb Evanston, Hb Val de Marne, Hb Utrecht, Hb Savaria, Hb Adana, and Hb Dartmouth were identified. The hematological profile and molecular basis of these ten alpha-chain variants and the phenotypic consequences of their interactions were discussed. The knowledge of the spectrum of alpha-globin variants present in the Iranian population is essential for the molecular diagnosis and prevention of hemoglobinopathies

13-bp deletion in the 3 untranslated region of the beta-globin gene causes beta-thalassemia major in compound heterozygosity with IVSII-1 mutation

To describe hematological and molecular features of a 13-bp deletion in the 3' untranslated region[3' UTR] of the beta-globin gene in carrier individuals and a compound heterozygous patient. Five members of an Iranian family of Persian ethnic origin were studied. Red blood cell indices and hemoglobin analysis were carried out according to standard methods. Genomic DNA was obtained from peripheral blood cells by salting-out procedures. beta-Globin gene amplification and DNA sequencing were performed. One patient had a 13-bp deletion in the 3' UTR of the beta-globin gene that causes the beta-thalassemia phenotype in combination with the IVSII-1 [G-A] mutation. The patient had inherited the IVSII-1 [G-A] mutation from his mother, while the second beta-globin gene [inherited paternally] had a 13-bp deletion at nucleotide 90 downstream of the termination codon [CD +90 del 13 bp].The patient's father and paternal grandmother, who are carriers of this deletion, had no hematological abnormalities. This case showed a patient with a 13-bp deletion in the 3' UTR of beta-globin gene that could cause a slight decrease in the stability of the mRNA, but did not have a hematological effect in the heterozygotes. The 13-bp deletion could be clinically important only in situations where beta-chain synthesis in trans is compromised

[Study of the association between estrogen receptor alpha gene expression in the levels of RNA and protein in primary breast tumors]

Estrogen receptor alpha protein status is determined by routine immunohistochemistry analysis in all malignant breast tumors. This assay has its limitations. RNA based techniques are potential complements for immunohistochemistry but it must be noticed that gene silencing may occur at different levels from RNA to protein. The aim of this study was the comparison of the results from these two assays and characterizing the tumors subgroup in which gene expression occurs at RNA level but the target protein is absent. 92 primary breast tumors including their clinical and IHC results were collected before treatment. Estrogen receptor gene expression of tumors was studied by Reverse Transcription Polymerase Chain Reaction [RT PCR]. In this assay, GAPDH was used as a reference gene. 36.6% of tumors with negative estrogen receptor protein showed gene expression at mRNA level. In this subgroup most of the patient were older than 50 years and in stages 3 or 4 of breast cancer and had poor prognosis according to Nottingham prognostic index. Most cases of the perineural invasion have been seen in this subgroup. It seems that RT-PCR assay would enable us to recognize a subgroup of breast tumors with poor prognosis which expresses RNA but not protein

Transient expression assay of [A]gamma-588 [A/G] mutations in the k562 cell line

In the previous study, we have shown that the presence of A allele at position -588 in [A]gamma -globin gene was highly frequent and closely associated with fetal hemoglobin elevation among beta-thalassemia intermedia patients. Therefore, we decided to investigate whether this allele [A allele at -588] could result in an increase in [A]gamma-globin gene expression to ameliorate the severity of the disease in thalassemia patients. Three constructs containing ji locus control region, [A]gamma -globin and beta-globin genes were designed and employed in the transient expression assay. The difference among constructs was in the promoter region of, [A]gamma -globin gene [A and G alleles at -588]. A construct with T to C base substitution at -175 of, [A]gamma -globin, created by site-directed mutagenesis, was selected as positive control. The K562 cell line was transfected with the above constructs. Subsequently, the expression of, [A]gamma -globin gene was determined by quantitative real-time reverse transcription-PCR. There was not a significant increase in the expression of, [A]gamma -globin gene in the construct containing A allele comparing the one with G allele at -588. -588 [A>G] mutation does not play a major role in regulation of, [A]gamma -globin gene, suggesting that other factors may be involved

frequency of DYT1 [GAG deletion] mutation in primary dystonia patients from Iran

To determine the frequency of DYT1 mutation in Iranian patients affected with primary dystonia. in this study, we investigated 60 patients with primary dystonia who referred to the Tehran Medical Genetics Laboratory [TMGL] to determine the deletional mutation of 904-906 del GAG in the DYT1 gene, DNA extracted from patients' peripheral blood was subjected to PCR-sequencing for exon 5 of the DYT1 gene. The collection of samples was based on random sampling. The deletional mutation of 904-906 del GAG in the DYT1 gene [15099 to 15101 based on reference sequence: NGJ308049.1] was identified in 11 patients [18.33%]. The average age of affected patients with this mutation was 13.64 +/- 7.4 years. Conclusion: It can be concluded that the DYT1 deletional mutation of 904-906 del GAG has a high frequency in Iranian patients in comparison with other non-Jewish populations. Therefore, this particular mutation may be the main representative of pathogenic DYT1 gene for a large proportion of Iranian patients with primary dystonia

Post catheter diagnostic coronary angiography thrombotic complications at femoral vascular access site- an ultrasound based study

To determine the frequency of atherosclerotic plaques in common femoral artery in patients undergoing coronary angiography. Identify any significant post procedure change in plaque morphology. Determine the number of patients who develop thrombosis at the access site. Descriptive study. The study was carried out in Radiology Department, Military Hospital, Rawalpindi from 10 Aug 2005 - 09 Feb 2006. The patients undergoing coronary angiography were included in the study. Doppler ultrasound of the right common femoral artery [vascular access site] was done prior to and following coronary angiography. The ultrasound examinations were performed on ALOKA Prosound SSD 5500 using 7.5 MHz linear array probe. Out of the 100 patients included in the study, atherosclerotic plaque was detected in 10 patients at the femoral access site. Out of these 10 patients, having a plaque at access site 01 patient developed a thrombus at the access site. The post procedure diameter of the femoral artery was significantly reduced. Despite the advancements in technique and equipment a thrombus can form at the vascular access site. Doppler ultrasonography proves an ideal diagnostic tool in evaluation of cases with suspected access site complications

Complications and interventions associated with epidural analgesia for postoperative pain relief in a tertiary care hospital

Epidural analgesia is one of the commonly used methods of postoperative pain control despite its associated complications. Early recognition and intervention is required to minimize the effect of these complications. Present audit was conducted to find out the incidence of complications and type of interventions required to change the outcome. The record of all the patients who had epidural catheter placed for postoperative pain management reviewed from the departmental acute pain management register. Parameters included level of insertion, drugs used, number of days infusion continued and complications like nausea, vomiting, motor block, sedation, dural tap, catheter pull out, hypotension and itching. In addition, the intervention done to manage these complications was also recorded. Total 1706 entries of epidurals were recorded in study period 2001 to 2007. The overall incidence of the complication was 26.6%. The common complications were motor block [13.4%], dural tap [1.2%], ineffective pain control [2.4%], accidental catheter pull outs [3.8%] and problems associated with the delivery system of drug [1.7%]. The 12% of patients required intervention for the particular complications. The regime was discontinued in 28%, drug concentration changed in 21.5% while the other modes of pain management were used in 19% of patients. 0.9% of patients required epidural blood patch while 2% of patients required catheterization for urinary retention. This audit shows the importance of regular assessment and early intervention to manage epidural related complications in improving outcome

Single lung ventilation in a young child for repair of coarctation of aorta

Single lung ventilation in small children is extremely challenging. In this case, a paediatric bronchial blocker was successfully inserted in a 19-month-old child to provide single lung ventilation using a modified insertion technique. It provided excellent working conditions during thoracotomy and our method of insertion may help in reducing the cost

Grown up Congenital Heart Disease patient presenting for non cardiac surgery: anaesthetic implications

Congenital heart disease patients surviving to adulthood have increased over the years due to various reasons. These patients are admitted in the hospital for non cardiac surgeries and other procedures more often than normal adult population. Management of grown up congenital heart disease patient presents a challenge during perioperative period for cardiologists, surgeons, intensivists and particularly for the anaesthetist. Management issues include psychological and physiological impact on the patient, complexity of defects, presence of previous palliative procedure, impact of anaesthetic agents on shunting and myocardium, endocarditis prophylaxis and associated extra cardiac anamolies