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1.
Int J Obstet Anesth ; 44: 33-39, 2020 11.
Article in English | MEDLINE | ID: mdl-32736124

ABSTRACT

BACKGROUND: The epidural anesthesia technique is a challenging skill to master. The Accreditation Council for Graduate Medical Education (ACGME) stipulates that anesthesiology residents must complete 40 epidural procedures by the end of junior residency. The rationale is unknown. The aim of this prospective study was to determine the minimum case experience required to demonstrate competence in performing obstetric combined spinal-epidural procedures among junior residents, using an objective statistical tool, the cumulative sum (CUSUM) analysis. METHODS: Twenty-four residents, with no prior experience performing epidurals, sequentially recorded all obstetric combined spinal-epidural procedures as a 'success' or 'failure', based on study criteria. Individual CUSUM graphs were plotted, with acceptable and unacceptable failure rates set at 20% and 35%, respectively. The number of procedural attempts necessary to demonstrate competence was determined. RESULTS: Twenty-four residents (mean (SD) age 29 (2) years) participated in the study. Median (IQR) number of procedures was 78 (66-85), with a median (IQR) success rate of 86% (82-89%). Nineteen of 24 residents required a median (IQR) of 40 (33-50) attempts to demonstrate competence. Five did not achieve procedural competence in the training period. The CUSUM graphs highlighted performance trends that required intervention. CONCLUSION: Competence was achieved by 19/24 residents after the ACGME-required case experience of 40 combined spinal-epidural procedures, based on a predefined acceptable failure rate of 20%. In our experience, CUSUM analysis is useful in monitoring technical performance over time and should be included as an adjunct assessment method for determining procedural competence.


Subject(s)
Anesthesia, Epidural/standards , Anesthesia, Obstetrical/standards , Anesthesia, Spinal/standards , Anesthesiology/standards , Clinical Competence/statistics & numerical data , Internship and Residency/statistics & numerical data , Adult , Anesthesia, Epidural/methods , Anesthesia, Obstetrical/methods , Anesthesia, Spinal/methods , Anesthesiology/methods , Female , Humans , Internship and Residency/methods , Male , Prospective Studies
2.
Int J Obstet Anesth ; 43: 114-117, 2020 08.
Article in English | MEDLINE | ID: mdl-32386993

ABSTRACT

The provision of safe obstetric anaesthesia services is essential during the COVID-19 global outbreak. The identification of the 'high-infection risk' parturient can be challenging especially with the rapidly changing risk criteria for COVID-19 'cases'. A multidisciplinary taskforce is required to review the infection control protocols and workflows for managing the parturient for labour analgesia and for caesarean section in order to minimize infection risk to healthcare staff and other parturients. A constant review of such processes is needed to enhance efficiency and to optimise use of finite resources. Good communication between health officials, institutional leadership and ground staff is essential for the dissemination of information.


Subject(s)
Anesthesia Department, Hospital/organization & administration , Anesthesia, Obstetrical , Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , COVID-19 , Cesarean Section , Coronavirus Infections/prevention & control , Disease Outbreaks , Female , Health Resources , Humans , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pregnancy , SARS-CoV-2 , Singapore/epidemiology
3.
Int J Obstet Anesth ; 39: 88-94, 2019 08.
Article in English | MEDLINE | ID: mdl-30852134

ABSTRACT

BACKGROUND: Task-centred learning forms the basis of procedural training in obstetric anaesthesia. We observed that our residents were not building their competence from experiential practice in the operating theatre. We used a broad-based framework to explore the challenges encountered by the residents and clinical supervisors in the learning and teaching of obstetric anaesthesia. METHODS: The study was conducted at the KK Women's and Children's Hospital, Singapore, from 1 December 2016 to 30 June 2017. A semi-structured interview format was used in the focus group and individual interviews. Information collection continued until data saturation was reached. The interviews were analysed and the challenges were identified. Fourteen residents and five clinical supervisors participated in the focus group and individual interviews respectively. FINDINGS: The operating theatre constituted a stressful learning and teaching environment for the participants. Five categories of challenges were identified: (1) clinical conditions, (2) concerns about maternal risk and outcomes, (3) reluctance of the residents to vocalise their learning needs, (4) poor feedback, and (5) lack of opportunities for inter-professional practice. These collective challenges reduced the quality of task-centred learning and the effectiveness of supervisor teaching. We described some strategies to overcome these challenges (dedicated trainee lists, obstetric anaesthesia reflective diary, active mentoring system and in-situ simulation). CONCLUSIONS: Our study described the challenges of obstetric anaesthesia training in the operating theatre environment in an Asian healthcare setting. Research is needed on the influence of supervisors' concern about maternal risks and their teaching behaviours.


Subject(s)
Anesthesia, Obstetrical , Anesthesiology/education , Adult , Female , Humans , Learning , Male , Middle Aged , Operating Rooms , Teaching
4.
Int J Obstet Anesth ; 28: 34-38, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27641087

ABSTRACT

BACKGROUND: The KK Women's and Children's Hospital is a tertiary obstetric unit with approximately 11000 deliveries per year. Epidural analgesia is used in about 40% of laboring women. We reviewed the incidence and management of post-dural puncture headache over a nine-year period. METHODS: A retrospective audit of labor epidural analgesia database records from 1 June 2005 to 31 May 2014 was conducted, identifying an "event" as an accidental dural puncture, an inadvertent intrathecal catheter insertion and/or development of a post-dural puncture headache. RESULTS: A total of 43434 epidural records were reviewed. Sixty-three events were identified (an incidence of 0.15%). Women had median age of 30years and median body mass index of 27.6kg/m2; 69.8% (44/63) delivered vaginally. Procedures performed by less experienced anesthesiologists and those performed outside office hours were associated with a higher incidence of accidental dural puncture. An intrathecal catheter was inserted in 52 of 58 women (89.7%). Headache developed in 24 of 38 (63.1%) women in whom there was a witnessed accidental dural puncture. Most women who developed post-dural puncture headache presented during the primary admission (36/39; 92.3%). Paracetamol and non-steroidal anti-inflammatory drugs were the most commonly prescribed medications. Six women (9.5%) received an epidural blood patch which led to resolution of headache. CONCLUSION: A retrospective audit over a nine-year period at a tertiary teaching hospital found the overall incidence of post-dural puncture headache and associated events to be 0.15%, with a decreasing trend coinciding with improvement in the teaching and supervision of trainees in labor epidural procedures.


Subject(s)
Clinical Audit/statistics & numerical data , Post-Dural Puncture Headache/epidemiology , Post-Dural Puncture Headache/therapy , Acetaminophen/therapeutic use , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Blood Patch, Epidural/statistics & numerical data , Clinical Competence/statistics & numerical data , Female , Humans , Incidence , Pregnancy , Retrospective Studies , Singapore/epidemiology , Tertiary Care Centers/statistics & numerical data
5.
J Wound Care ; 25(7): 393-7, 2016 Jul 02.
Article in English | MEDLINE | ID: mdl-27410393

ABSTRACT

UNLABELLED: Management and treatment of acute severe diabetic foot disease in patients with suboptimal glycaemic control is a critical issue in wound repair. This paper discusses the clinical efficacy of an aggressive surgical intervention combined with targeted use of regenerative medical therapies in limb preservation. Negative pressure wound therapy (NPWT), platelet-rich plasma (PRP), bilayered acellular matrix grafting and split-thickness skin grafting were combined to treat a patient with diabetes, foot necrotising fasciitis and gaseous gangrene. The wound was completely healed. The clinical outcome revealed that a multi-intervention strategy could be effective for large necrotising fasciitis wounds. Early clinical observation, suggests aggresive surgical intervention preserving intact tissue and targeted use of new regenerative technologies can lead to preservation of a limb. DECLARATION OF INTEREST: The authors have received no financial support for the material presented in this study outside of the scope of standard patient care reimbursement. This work was supported by the National Natural Science Foundation of China (NO. 81500596) awarded to Dr Wuquan Deng.


Subject(s)
Diabetic Foot/therapy , Negative-Pressure Wound Therapy , Platelet-Rich Plasma , Skin Transplantation , Wound Healing/physiology , Acellular Dermis , Adult , China , Humans , Male , Treatment Outcome
6.
Vox Sang ; 110(1): 36-50, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26178308

ABSTRACT

BACKGROUND: A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals. METHODS: Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients. RESULTS: There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation. CONCLUSION: This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider.


Subject(s)
Blood Transfusion/methods , Clinical Protocols , Practice Guidelines as Topic , Adult , Blood Transfusion/standards , Hemorrhage/epidemiology , Hemorrhage/therapy , Hospitals/statistics & numerical data , Humans , Singapore , Transfusion Reaction
7.
Cell Death Dis ; 6: e1646, 2015 Feb 19.
Article in English | MEDLINE | ID: mdl-25695599

ABSTRACT

Billions of inflammatory leukocytes die and are phagocytically cleared each day. This regular renewal facilitates the normal termination of inflammatory responses, suppressing pro-inflammatory mediators and inducing their anti-inflammatory counterparts. Here we investigate the role of the receptor tyrosine kinase (RTK) Mer and its ligands Protein S and Gas6 in the initial recognition and capture of apoptotic cells (ACs) by macrophages. We demonstrate extremely rapid binding kinetics of both ligands to phosphatidylserine (PtdSer)-displaying ACs, and show that ACs can be co-opsonized with multiple PtdSer opsonins. We further show that macrophage phagocytosis of ACs opsonized with Mer ligands can occur independently of a requirement for αV integrins. Finally, we demonstrate a novel role for Mer in the tethering of ACs to the macrophage surface, and show that Mer-mediated tethering and subsequent AC engulfment can be distinguished by their requirement for Mer kinase activity. Our results identify Mer as a receptor uniquely capable of both tethering ACs to the macrophage surface and driving their subsequent internalization.


Subject(s)
Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Apoptosis/genetics , Apoptosis/physiology , Blotting, Western , Cells, Cultured , Flow Cytometry , Humans , Integrin alphaV/metabolism , Macrophages/metabolism , Microscopy, Electron, Scanning , Phagocytosis/genetics , Phagocytosis/physiology , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/genetics , c-Mer Tyrosine Kinase
8.
Article in English | MEDLINE | ID: mdl-19963794

ABSTRACT

In this paper we present further results of our asynchronous and non-invasive BMI for the continuous control of an intelligent wheelchair. Three subjects participated in two experiments where they steered the wheelchair spontaneously, without any external cue. To do so the users learn to voluntary modulate EEG oscillatory rhythms by executing three mental tasks (i.e., mental imagery) that are associated to different steering commands. Importantly, we implement shared control techniques between the BMI and the intelligent wheelchair to assist the subject in the driving task. The results show that the three subjects could achieve a significant level of mental control, even if far from optimal, to drive an intelligent wheelchair.


Subject(s)
Brain/pathology , Electroencephalography/methods , Man-Machine Systems , Wheelchairs , Algorithms , Equipment Design , Humans , Neural Networks, Computer , Oscillometry/methods , Pattern Recognition, Automated , Reproducibility of Results , Robotics , Telemetry , User-Computer Interface
9.
Clin Neurophysiol ; 119(9): 2159-69, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18621580

ABSTRACT

OBJECTIVE: To assess the feasibility and robustness of an asynchronous and non-invasive EEG-based Brain-Computer Interface (BCI) for continuous mental control of a wheelchair. METHODS: In experiment 1 two subjects were asked to mentally drive both a real and a simulated wheelchair from a starting point to a goal along a pre-specified path. Here we only report experiments with the simulated wheelchair for which we have extensive data in a complex environment that allows a sound analysis. Each subject participated in five experimental sessions, each consisting of 10 trials. The time elapsed between two consecutive experimental sessions was variable (from 1h to 2months) to assess the system robustness over time. The pre-specified path was divided into seven stretches to assess the system robustness in different contexts. To further assess the performance of the brain-actuated wheelchair, subject 1 participated in a second experiment consisting of 10 trials where he was asked to drive the simulated wheelchair following 10 different complex and random paths never tried before. RESULTS: In experiment 1 the two subjects were able to reach 100% (subject 1) and 80% (subject 2) of the final goals along the pre-specified trajectory in their best sessions. Different performances were obtained over time and path stretches, what indicates that performance is time and context dependent. In experiment 2, subject 1 was able to reach the final goal in 80% of the trials. CONCLUSIONS: The results show that subjects can rapidly master our asynchronous EEG-based BCI to control a wheelchair. Also, they can autonomously operate the BCI over long periods of time without the need for adaptive algorithms externally tuned by a human operator to minimize the impact of EEG non-stationarities. This is possible because of two key components: first, the inclusion of a shared control system between the BCI system and the intelligent simulated wheelchair; second, the selection of stable user-specific EEG features that maximize the separability between the mental tasks. SIGNIFICANCE: These results show the feasibility of continuously controlling complex robotics devices using an asynchronous and non-invasive BCI.


Subject(s)
Brain/physiology , Robotics , User-Computer Interface , Wheelchairs , Brain Mapping , Electroencephalography/methods , Humans
10.
Minerva Anestesiol ; 74(3): 77-85, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18288070

ABSTRACT

Neuraxial block for labor analgesia is widely accepted and highly effective. Much progress has been achieved in terms of providing safer and more efficacious analgesia. Emphasis has been placed on maternal autonomy and individualization of therapy. The introduction of the combined spinal-epidural technique in the labor ward has afforded excellent rapid onset analgesia and minimal impediment to maternal mobility. Newer enantiopure amide local anesthetics, like ropivacaine and levobupivacaine, have also been introduced to enhance the safety of epidural analgesia with respect to cardiotoxicity. The introduction of the computer-assisted approach to provide a more interactive background infusion could potentially refine the delivery of patient-controlled epidural analgesia. The enhanced effectiveness of synchronized basal automated boluses has also been exploited for patient-controlled epidural analgesic systems. The quest to provide seamless analgesia that empowers the laboring parturient in a cost effective way continues to be a developing area of research.


Subject(s)
Analgesia, Obstetrical/methods , Nerve Block/methods , Algorithms , Analgesia, Epidural , Female , Humans , Pregnancy
11.
Proc Natl Acad Sci U S A ; 103(49): 18603-8, 2006 Dec 05.
Article in English | MEDLINE | ID: mdl-17132737

ABSTRACT

Craniosynostosis, the fusion of one or more of the sutures of the skull vault before the brain completes its growth, is a common (1 in 2,500 births) craniofacial abnormality, approximately 20% of which occurrences are caused by gain-of-function mutations in FGF receptors (FGFRs). We describe a genetic and pharmacological approach for the treatment of a murine model system of Crouzon-like craniosynostosis induced by a dominant mutation in Fgfr2c. Using genetically modified mice, we demonstrate that premature fusion of sutures mediated by Crouzon-like activated Fgfr2c mutant is prevented by attenuation of signaling pathways by selective uncoupling between the docking protein Frs2alpha and activated Fgfr2c, resulting in normal skull development. We also demonstrate that attenuation of Fgfr signaling in a calvaria organ culture with an Fgfr inhibitor prevents premature fusion of sutures without adversely affecting calvaria development. These experiments show that attenuation of FGFR signaling by pharmacological intervention could be applied for the treatment of craniosynostosis or other severe bone disorders caused by mutations in FGFRs that currently have no treatment.


Subject(s)
Craniosynostoses/genetics , Craniosynostoses/prevention & control , Mutagenesis, Site-Directed , Receptor, Fibroblast Growth Factor, Type 2/genetics , Receptor, Fibroblast Growth Factor, Type 2/metabolism , Signal Transduction/genetics , Animals , Craniofacial Dysostosis/genetics , Craniofacial Dysostosis/pathology , Craniofacial Dysostosis/prevention & control , Craniosynostoses/pathology , Gene Expression Regulation , Mice , NIH 3T3 Cells , Receptor, Fibroblast Growth Factor, Type 2/physiology
12.
Singapore Med J ; 45(11): 509-16, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15510321

ABSTRACT

In recent years, there has been a paradigm shift from an inpatient to outpatient preanaesthesia evaluation. This has been driven by rising healthcare costs and the increasing popularity of ambulatory and same-day admission surgery. These outpatient preanaesthesia clinics play an important role in enhancing the cost-effectiveness of the perioperative process. This review describes the structure of modern outpatient preanaesthesia evaluation clinics, and the associated benefits, limitations and controversies.


Subject(s)
Anesthesiology/organization & administration , Outpatient Clinics, Hospital/organization & administration , Preoperative Care/trends , Cost Control , Diagnostic Tests, Routine , Humans , Length of Stay , Nurse Clinicians
13.
Int J Obstet Anesth ; 13(4): 221-6, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15477050

ABSTRACT

We conducted a retrospective study of all cases of cesarean section at the KK Women's and Children's Hospital over a one-year period from September 1, 2002 to August 31, 2003, with the aim of evaluating current anesthetic practice. These cases were identified using hospital databases and relevant data was extracted from clinical notes. There were 14244 deliveries during the study period with a cesarean section rate of 25.2% (3583 cases). Of these, 20.4% (732 cases) were performed under general anesthesia. Maternal request was the chief reason for general anesthesia, especially among elective cases. Regional block failure accounted for 16% of the general anesthesia cases performed or 4.0% of the total regional techniques attempted. Regional block failure rate was highest for emergency cases in which an indwelling labor epidural catheter was used to provide surgical anesthesia via a bolus top-up. General anesthesia still has a definite place for cesarean delivery despite the predominant use of regional techniques in our institution.


Subject(s)
Anesthesia, General , Anesthesia, Obstetrical , Cesarean Section , Adult , Anesthesia, Conduction , Anesthesia, General/adverse effects , Anesthesia, Obstetrical/adverse effects , Data Collection , Female , Hospitals, Maternity , Humans , Pregnancy , Retrospective Studies , Singapore , Treatment Failure
14.
AIDS ; 15(13): 1665-70, 2001 Sep 07.
Article in English | MEDLINE | ID: mdl-11546941

ABSTRACT

OBJECTIVES: Successful highly active antiretroviral therapy (HAART) is usually associated with a rapid decline in HIV plasma RNA levels and a gradual increase in CD4 T cells. We examined whether changes in cytokine production and profile precede other immunological changes and whether these might occur in temporal association with plasma HIV RNA changes. DESIGN AND METHODS: Eleven HIV-1-infected patients were enrolled into a prospective cohort study; eight patients were naive to antiretroviral therapy. Blood samples were collected pre-therapy (week 0) and at 1, 2, and 3 weeks post-initiation of therapy. RESULTS: All 11 patients enrolled remained on triple HAART for 1 week, eight for 2 weeks, and six for > or = 3 weeks. When compared to week 0, these patients had a > or = 2-log10 decline in HIV plasma RNA levels and/or a decline to < or = 400 copies/ml by week 3 of therapy (p = 0.004). The numbers and percentages of CD4 and CD8 T cells, and the percentage of naive, memory, and activated T cells did not change significantly between weeks 0 and 1 or 0 and 3. Of all the immune parameters examined only: the percentage of CD4 T cells spontaneously producing tumor necrosis factor (TNF)-alpha (median, 2.4 versus 0.5% P = 0.025); the percentage of CD8 T cells spontaneously producing TNF-alpha (median, 0.6 versus 0.2% P = 0.037); and the percentage of CD3 T cells spontaneously producing interleukin-4 (median, 1.8 versus 0.8% P = 0.004) changed significantly between weeks 0 and 3. CONCLUSIONS: In these patients, decreases in the percentage of T cells spontaneously producing TNF-alpha or interleukin-4 preceded changes in CD4 T cells. If confirmed by others, these observations may be useful as early predictors of response to and early failure of HAART.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , HIV-1/physiology , Interleukin-4/biosynthesis , Tumor Necrosis Factor-alpha/biosynthesis , Adult , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cohort Studies , HIV Infections/virology , Humans , Immunophenotyping , Male , Prospective Studies
16.
J Acquir Immune Defic Syndr ; 27(2): 105-15, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11404531

ABSTRACT

OBJECTIVE: To measure CCR5 and CXCR4 chemokine receptor expression on CD4 and CD8 T cells in HIV-1 infection and to relate levels to the distribution of CD45RO memory and CD45RA-naive subsets, measures of disease activity, and response to highly active antiretroviral therapy (HAART). DESIGN: Fourteen untreated HIV-1-infected patients, 18 patients at 3-to 4-weeks after beginning HAART, and 35 uninfected control subjects were studied. METHODS: Four-color cytofluorometry with appropriate conjugated monoclonal antibodies (mAbs) was performed to define CD45RA and CD45RO subsets of CD4 and CD8 T cells and measure their expression of CCR5, CXCR4, and CD38. RESULTS: HIV-1-infected patients had higher CCR5 levels and lower CXCR4 levels on CD4 and CD8 T cells and their CD45RO/CD45RA subsets than control subjects did. However, CCR5 elevation was statistically significant only for CD4 T cells and their subsets, and CXCR4 depression was significant for CD8 T cells and their subsets (and for CD4:CD45RO cells). The elevation of CCR5 and depression of CXCR4 were not due to shifts in CD45RO/CD45RA subset proportions but to upregulation or downregulation within the subsets. CCR5 elevation on CD4 T cells was significantly restored toward normal by HAART, but the CXCR4 depression was not. CCR5 expression but not CXCR4 expression correlated with other measures of immunodeficiency (CD4 T-cell levels), active infection (viral load), and cellular activation (CD38). CONCLUSIONS: CCR5 elevation is a concomitant of immune activation and viral replication that occurs in HIV-1 infection, but the relation of CXCR4 depression to severity of infection, disease progression, and response to therapy remains undefined.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , Receptors, CCR5/metabolism , Receptors, CXCR4/metabolism , T-Lymphocytes/immunology , Adult , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/virology , HIV-1/physiology , Humans , Immunologic Memory , Leukocyte Common Antigens/metabolism , Viral Load
18.
Am J Gastroenterol ; 96(12): 3274-80, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11774936

ABSTRACT

OBJECTIVES: In patients with Zollinger-Ellison syndrome (ZES) or other conditions requiring oral doses of proton pump inhibitors, it frequently becomes necessary to use parenterally administered gastric acid inhibitors. However, i.v. histamine-2 receptor antagonists are not effective at usual doses and lose their effectiveness because of tachyphlaxis. With the approval in the United States of i.v. pantoprazole, a substituted benzimidazole available in i.v. formulation, it will become possible to acutely manage gastric acid secretion in the acute care setting of a hospital. This study was developed to monitor the safety and establish the efficacy of i.v. pantoprazole as an alternative to oral proton pump inhibitors for the control of gastric acid hypersecretion in patients with ZES. METHODS: The efficacy of replacing oral PPI therapy with i.v. pantoprazole was evaluated in 14 ZES patients. After study enrollment, patients taking their current doses of oral PPI (omeprazole or lansoprazole) were switched to pantoprazole i.v. for 6 days during an 8-day inpatient period in the clinical research center. Effective control was defined as an acid output (AO) of < 10 mEq/h (< 5 mEq/h in patients with prior gastric acid-reducing surgery). RESULTS: The mean age of the 14 patients enrolled in the study was 52.4 yr (range = 38-67). Mean basal AO was 0.55 +/- 0.32 mEq/h and mean fasting gastrin was 1089 pg/ml (range = 36-3720). Four patients were also diagnosed with the multiple endocrine neoplasia type I syndrome, nine were male, and two had previously undergone acid-reducing surgery. Before study enrollment, gastric acid hypersecretion was controlled in nine of 14 patients with omeprazole (20-200 mg daily) and five of 14 with lansoprazole (30-210 mg daily). In the oral phase of the study all patients had adequate control of gastric acid secretion, with a mean AO of 0.55 +/- 0.32 mEq/h (mean +/- SEM). Thereafter, 80 mg of i.v. pantoprazole was administered b.i.d. for 7 days by a brief (15 min) infusion and the dose was titrated upward to a predetermined maximum of 240 mg/24 h to control AO. A dose of 80 mg b.i.d. of i.v. pantoprazole controlled AO in 13 of 14 of the patients (93%) for the duration of the study (p > 0.05 compared to baseline values for all timepoints). One sporadic ZES patient (oral control value = 0.65 mEq/h on 100 mg of omeprazole b.i.d. p.o.) was not controlled with 80 mg of i.v. pantoprazole b.i.d. and dosage was titrated upward to 120 mg b.i.d. after day 2. CONCLUSIONS: There were no serious adverse events observed. Intravenous pantoprazole provides gastric acid secretory control that is equivalent to the acid suppression observed with oral proton pump inhibitors. Most ZES patients (93%) maintained effective control of AO previously established with oral PPIs when switched to 80 mg of i.v. pantoprazole b.i.d.; however, for difficult-to-control patients, doses > 80 mg b.i.d. may be required.


Subject(s)
Benzimidazoles/administration & dosage , Enzyme Inhibitors/administration & dosage , Gastric Acid/metabolism , Sulfoxides/administration & dosage , Zollinger-Ellison Syndrome/drug therapy , Zollinger-Ellison Syndrome/metabolism , 2-Pyridinylmethylsulfinylbenzimidazoles , Administration, Oral , Adult , Aged , Benzimidazoles/adverse effects , Benzimidazoles/therapeutic use , Dose-Response Relationship, Drug , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/therapeutic use , Female , Humans , Injections, Intravenous , Male , Middle Aged , Omeprazole/analogs & derivatives , Pantoprazole , Proton Pump Inhibitors , Retreatment , Sulfoxides/adverse effects , Sulfoxides/therapeutic use
19.
Gastroenterology ; 118(4): 696-704, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10734021

ABSTRACT

BACKGROUND & AIMS: Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings). METHODS: We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output >10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours. RESULTS: The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type I, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9). In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7). No serious or unexpected adverse events were observed. CONCLUSIONS: Intravenous pantoprazole, 160-240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients.


Subject(s)
Anti-Ulcer Agents/therapeutic use , Benzimidazoles/administration & dosage , Gastric Acid/metabolism , Sulfoxides/administration & dosage , Zollinger-Ellison Syndrome/drug therapy , Zollinger-Ellison Syndrome/metabolism , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Aged , Benzimidazoles/adverse effects , Benzimidazoles/therapeutic use , Female , Humans , Injections, Intravenous , Male , Middle Aged , Omeprazole/analogs & derivatives , Pantoprazole , Sulfoxides/adverse effects , Sulfoxides/therapeutic use , Treatment Outcome
20.
Am J Gastroenterol ; 95(3): 626-33, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10710049

ABSTRACT

OBJECTIVE: The aim of this study was to assess the ability of pantoprazole to maintain gastric acid suppression in patients with gastroesophageal reflux disease who are switched from an oral (p.o.) to an intravenous (i.v.) dosage form. METHODS: A total of 65 patients with gastroesophageal reflux disease were administered either 40 or 20 mg of p.o. pantoprazole daily for 10 days, then were switched to either a matching dose of i.v. pantoprazole or to placebo for 7 days. Acid output (basal and maximal) was measured at the end of the p.o. treatment period and on the first and last days of i.v. therapy. In the primary efficacy analysis, the acid output values at the end of the p.o. pantoprazole treatment were compared with those at the end of the i.v. treatment. Safety was monitored by periodic vital sign measurements, clinical laboratory evaluations, ophthalmic examinations, electrocardiograms, and reports of adverse events. The data were tested by an analysis of covariance and by Wilcoxon signed rank and t tests. RESULTS: Maximal acid output (mean +/- SD) in the 40 mg and 20 mg pantoprazole group after p.o. treatment was 6.5 +/- 5.6 mEq/h and 14.5 +/- 15.5 mEq/h, respectively; whereas, at the end of the i.v. treatment period, the values were 6.6 +/- 6.3 mEq/h and 11.1 +/- 10.2 mEq/h, respectively. In patients given i.v. placebo, acid output was significantly (p < 0.05) increased to 29.2 +/- 13.0 mEq/h by day 7. Both p.o. and i.v. pantoprazole dosage forms had similar favorable safety and tolerability profiles. CONCLUSIONS: The p.o. and i.v. formulations of pantoprazole (40 and 20 mg) are equivalent in their ability to suppress gastric acid output. The i.v. form of pantoprazole offers an alternative for gastroesophageal reflux disease patients who are unable to take the p.o. formulation.


Subject(s)
Anti-Ulcer Agents/administration & dosage , Benzimidazoles/administration & dosage , Gastric Acid/metabolism , Gastroesophageal Reflux/drug therapy , Sulfoxides/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles , Administration, Oral , Adult , Anti-Ulcer Agents/adverse effects , Benzimidazoles/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Gastric Acidity Determination , Gastroesophageal Reflux/physiopathology , Humans , Infusions, Intravenous , Male , Middle Aged , Omeprazole/analogs & derivatives , Pantoprazole , Sulfoxides/adverse effects , Treatment Outcome
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