This document discusses the clinical benefits of Diprivan (propofol). It notes that Diprivan provides:
1) Smooth, rapid induction of anesthesia within 30-60 seconds.
2) Easy control and maintenance of anesthesia at infusion rates of 4-12 mg/kg/h.
3) Prompt, clear-headed recovery with rapid return of cognitive and motor function.
Recovery from Diprivan anesthesia is characterized by a low risk of postoperative nausea and vomiting compared to inhalational agents. Overall, Diprivan provides good quality induction, maintenance, and recovery from anesthesia.
TIVA is a technique of anesthesia involving the induction and maintenance of anesthetic state with IV drugs alone. Shorter context sensitivity half time anesthetic agents like propofol is the universally accepted induction agent of choice widely used as a component of TIVA.
Robotic surgeries are becoming most popular in field of surgical departments due to its precision of hand in many cancer surgeries. Anaesthesia in these places are quite challenging due to lack place to move , a meticulous vigilance is always required for safety of patient and conduct safe Anesthesia
TIVA is a technique of anesthesia involving the induction and maintenance of anesthetic state with IV drugs alone. Shorter context sensitivity half time anesthetic agents like propofol is the universally accepted induction agent of choice widely used as a component of TIVA.
Robotic surgeries are becoming most popular in field of surgical departments due to its precision of hand in many cancer surgeries. Anaesthesia in these places are quite challenging due to lack place to move , a meticulous vigilance is always required for safety of patient and conduct safe Anesthesia
Short description about awake craniotomy, its indications, contraindications, complications,various techniques of providing awake craniotomy and drugs used.
Humidifiers in anaesthesia and critical careTuhin Mistry
Humidification of inhaled gases has been standard of care during mechanical ventilation in anaesthesia and intensive care. Active & Passive humidification devices have rapidly evolved. basic knowledge of the mechanisms of action of each of these devices, as well as their advantages and disadvantages, becomes a necessity for anaesthesiologists and intensivists.
Short description about awake craniotomy, its indications, contraindications, complications,various techniques of providing awake craniotomy and drugs used.
Humidifiers in anaesthesia and critical careTuhin Mistry
Humidification of inhaled gases has been standard of care during mechanical ventilation in anaesthesia and intensive care. Active & Passive humidification devices have rapidly evolved. basic knowledge of the mechanisms of action of each of these devices, as well as their advantages and disadvantages, becomes a necessity for anaesthesiologists and intensivists.
Venture Design Workshop: Business Model CanvasAlex Cowan
These slides support the various workshops I do and my online curriculum in two principal places:
1. Business Model Canvas Tutorial
This is a more fully articulated instructional, complete with templates: bit.ly/nicebmc.
2. Startup Sprints
This is a structured self-service for Venture Design/new venture creation: bit.ly/startupsprints.
Evaluating the cost to benefit ratio of a Drug Delivery platformBhaswat Chakraborty
This talk calls for a tall order of understanding of the patient needs, techno-innovative and economic aspects of drug delivery platform technologies and in turn making sound decisions in research & development, administration and policy making. In general, therapeutic effect of a drug is determined by its potency as well as by the efficiency of its delivery to the site of action. Thus, therapeutic effects of many drugs are improved and controlled through the use of appropriate new drug delivery systems (NDDS). Often this advantage is associated with the added benefit of improved side effects and patient compliance for most NDDS. NDDS cover a wide range of technologies and routes of administration, such as oral, buccal-mucosal, ophthalmic, transdermal, pulmonary and colonic – to name a few.
Understanding the key patient needs and the resolve of devising the best delivery formulations have revolutionized the platform technologies. For example, in oral modified release (MR) technology, the key need is to optimize bioavailability with much fewer dosing frequency, whereas in ophthalmic MRs, the principal requirements are absence of local toxicity, tolerance, ease of dispensing, sterility, and osmolarity, etc. In this context, therapeutic categories are very relevant (e.g., the challenges and accuracy in technology development in ophthalmic preparation are steeper than oral preparations). For pulmonary delivery systems, the release of the drug in pulmonary tract is more important and beneficial for the patients than controlling the delivery. Similarly, achieving high local concentrations is the main goal in colonic and vaginal technologies.
Economic values or improvement in benefit-cost ratio in NDDS come not only from better addressing patient needs (efficacy enhancement, reduced dosing and side effects etc.) and compliance. Economic benefits are explicit in patent extension, increased market share and decreased costs). These benefits are obvious. Subtle and non-obvious benefits become apparent upon thorough cost effectiveness and cost utility analysis of many NDDS technologies. The speaker will give a few examples of substantial gains in quality adjusted life years when a drug was delivered through a delivery technology.
Suppliers and Exporters of Emergency and Transport Ventilator, Spencer Base Stretcher, Yellow Rolling Stretcher With Trendelenburg, Scoop Stretcher, Suresigns Vm8, Suresigns Vm3.
The Thora-3DI™ measures regional pulmonary contributions in a non-contact, non-invasive methodology, providing rich lung function information. The mobile measurement platform allows for assessment at the patient bedside. Earlier thoracic post-surgical evaluations are possible for patients that cannot be transferred to a pulmonary function testing environment.
PneumaCare is a Cambridge (UK)-based company providing clinicians with respiratory diagnostic and monitoring equipment using novel 3D-imaging technology. The company’s PneumaCare’s product family are revolutionary non-contact respiratory assessment systems that have the advantage of being able to provide richer information on a broader patient population, both swiftly and relatively easily.
Thora-3DI™ and PneumaScan™ are already being used in clinics, pre- and post-operative assessments, drug testing, and device development by both public and private health care providers. Further applications of PneumaCare’s proprietary Structured Light Plethysmography technology, developed in close partnership
with the clinical community, include home care, neonatal, critical care,
and rehabilitation applications.
manufacturing, supplying and exporting Life Saving Medical Devices and Disposables such as 3 Way Stopcock, Extension Lines with 3 way Stopcock, Three Way Stopcock, Paediatric & Neonatal Extension Lines, Pressure Monitoring Lines, Disposable Diaphragm Domes, Disposable Pressure Transducer, Continuous Flush / Flow Devices...
James Shaw & Jon Chapman, AstraZeneca on 'Assessing the Benefits and Risks of...eyefortransport
James Shaw & Jon Chapman, AstraZeneca speak on 'Assessing the Benefits and Risks of using Seafreight' at the 7th European 3PL Summit in Brussels, November 25th 2009.
To download all of the slides from the conference for free visit www.3PLsummit.com/eu_2009ppts
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
3. Target Controlled Infusion (TCI)
in anaesthetic practice
Convenience and control
of intravenous anaesthesia with ‘Diprivan’
propofol
New edition 1999
ANAESTHESIA
4. ‘Diprifusor’ (TCI Software/Subsystem/System)
has been developed to further enhance the
convenience and control of intravenous anaesthesia
with ‘Diprivan’. ‘Diprifusor’ is incorporated in
anaesthesia syringe pumps manufactured by
SIMS Graseby, Fresenius Vial and ALARIS
Medical Systems.
Further information about anaesthesia syringe pumps incorporating
‘Diprifusor’ is available from the manufacturers
SIMS Graseby Limited
Colonial Way
Watford
Herts, UK
‘Diprivan’, ‘Diprifusor’ and the stylized D with arrow logo are Fresenius Vial SA
trade marks of the AstraZeneca group of companies. Le Grand Chemin
38590 Brézins
Further information about ‘Diprivan’ and clinical aspects of France
‘Diprifusor’ TCI is available on request
ALARIS Medical Systems
AstraZeneca The Crescent, Jays Close
Alderley House, Alderley Park Basingstoke
Macclesfield, Cheshire, UK Hants, UK
5. Contents
Introduction 1 Documentation 31
– pump manufacturers
‘Diprivan’ 3–8 – AstraZeneca
Pharmacokinetic properties 4 Principles of setting and adjusting target concentrations 32
Clinical benefits 6
– quality of induction ‘Diprifusor’ TCI – clinical trials 35–53
– quality of maintenance Overview of clinical programme 36
– quality of recovery Accuracy of ‘Diprifusor’ TCI 37
– control of the depth of anaesthesia
Target Controlled Infusion (TCI) 9–15 – measurement of predictive performance
Development of concept and terminology 10 Anaesthetic effects of ‘Diprivan’ administered
– acronyms by ‘Diprifusor’ TCI 39
– key components – induction time
– considerations for commercial development – quality of induction
– defining TCI for anaesthesia – quality of maintenance
Benefits of TCI 12 – haemodynamic effects
– convenience in use – recovery times
– control of anaesthesia Wide range of adult patients 47
– other benefits – characteristics of study population,
TCI systems for ‘Diprivan’ 15 types of surgery and other drugs
– prototype ‘Diprifusor’ TCI systems – additional experience
– other prototype TCI systems for ‘Diprivan’ Tolerability profile of ‘Diprifusor’ TCI 48
– extensive experience – adverse events
– equipment reliability
‘Diprifusor’ TCI – practical aspects 17–33 User surveys with ‘Diprifusor’ TCI 49
General requirements for use of ‘Diprifusor’ TCI 18 – familiarisation of anaesthetists
‘Diprivan’ Pre-Filled Syringe (PFS) 19 – preference of anaesthetists
– assembly and aseptic precautions European multicentre study 51
– recognition tag in finger grip – preference of anaesthetists
‘Diprifusor’ TCI System 22 – induction and maintenance
– ‘Diprifusor’ TCI Subsystem – tolerability
– ‘Diprifusor’ TCI Software
– installation specification ‘Diprifusor’ TCI – main points 54–55
Syringe pumps incorporating ‘Diprifusor’ 24
– general principles References 56–57
– Graseby 3500 Anaesthesia Syringe Pump TCI Glossary 58–59
– Vial Médical Master TCI unit for Pilot Anaesthesia
syringe pump ‘Diprivan’ International Pocket inside
– ALARIS IVAC TIVA TCI syringe pump Prescribing Information back cover
6.
7. 1
Introduction
Many advances in anaesthesia have arisen from developments in Manual control of ‘Diprivan’ infusion for maintenance of
pharmacology (e.g. improved drugs) or technology (e.g. improved anaesthesia is sometimes viewed as “not as easy” as using a
mode of administration). The introduction of a new drug has vaporizer with an inhalational agent. There is, therefore, a general
often been the stimulus for the gradual development of more need for a more convenient method for infusing intravenous
precise delivery systems. agents.
Historically, inhalational anaesthesia developed from inter- Target Controlled Infusion (TCI) systems have been
mittent administration using a Schimmelbusch mask to continuous developed to provide improved convenience and control during
administration using a vaporizer so as to provide a steady depth of intravenous anaesthesia. The basic principle is that the anaesthetist
anaesthesia. Further refinements included the introduction of sets and adjusts the target blood concentration – and depth of
vaporizers with automatic compensation for changes in pressure anaesthesia – as required on clinical grounds. Infusion rates are
and temperature. Measurement of end-tidal partial pressure of altered automatically according to a validated pharmacokinetic
volatile drugs is an example of drug delivery based on an estimate model.
of target concentration. The basic principle is that the vaporizer ‘Diprifusor’ (TCI Software/Subsystem/System) for ‘Diprivan’
setting – and target concentration – is adjusted on clinical grounds is such a development. ‘Diprifusor’ is the first commercially
to provide optimum control of anaesthesia. available TCI system and is incorporated in syringe pumps from
Similarly with intravenous anaesthesia, the development of major manufacturers. ‘Diprifusor’ is designed to be as convenient
delivery systems has lagged behind that of drug development. to use as a vaporizer; the skills required in varying target blood
Intermittent administration of bolus doses is still common. Infusion concentration according to response have been learned during
pumps do allow the administration of a wide range of infusion administration of volatile agents from a calibrated vaporizer.
rates as well as bolus delivery. But maintenance of optimum This monograph reviews aspects of ‘Diprivan’ relevant to TCI
anaesthetic conditions is difficult whenever drug is titrated as well as outlining the principles of TCI before summarising
according to the changing needs of the patient. Frequent practical information and clinical studies of ‘Diprifusor’ TCI for
recalculations of infusion rate may be required with corresponding induction and maintenance of anaesthesia in adult patients.
“manual” alterations to the pump controls.
‘Diprivan’ (propofol) was introduced in 1986 as an intravenous
anaesthetic agent for the induction and maintenance of general
anaesthesia. Widespread clinical experience with ‘Diprivan’ has
established the benefits relating to the quality of control of
anaesthesia and the quality of recovery. Onset and offset of
anaesthetic effects are rapid and reliable. ‘Diprivan’ offers rapid
emergence, a low incidence of postoperative nausea and vomiting
(PONV) and a potential reduction in time to discharge. Total The terms manually-controlled infusion, manual infusion and
intravenous anaesthesia (TIVA) based on ‘Diprivan’ has the general manual control are used to designate manual adjustment of infusion rates
advantage of avoiding occupational exposure to inhalational agents. for anaesthesia syringe pumps administering ‘Diprivan’.
9. 3
‘Diprivan’
The distinct pharmacokinetic profile and clinical benefits
of ‘Diprivan’ were major factors in the development of
‘Diprifusor’ as an improved delivery system over manual
control of infusion.This section summarises these aspects
of ‘Diprivan’.
10. 4
Pharmacokinetic properties
Target Controlled Infusion (TCI) is a logical approach to the After a bolus dose, there is a rapid, initial distribution phase
development of improved administration techniques for an which represents distribution to highly perfused organs such as
intravenous anaesthetic agent. TCI is based on an understanding the brain (effect site). This is followed by a slower, second phase
of the agent’s pharmacokinetic properties. representing redistribution to less well perfused tissues such as
The pharmacokinetics of ‘Diprivan’ have been evaluated muscle. Significant metabolism occurs during the second phase.
extensively in a variety of disease states and patient groups after Recovery from anaesthesia is due to extensive redistribution
either bolus doses or continuous infusions.1 from the brain and to metabolic clearance.
‘Diprivan’ undergoes rapid and extensive distribution – and The decline of blood concentrations after a bolus dose or
rapid metabolic clearance. termination of infusion can best be described by an open, three-
Figure 1. Open, three-compartment pharmacokinetic model: schematic representation
keo Intravenous infusion
5 10 15 20 25 30 35 40 45 50
Drug equilibrates between
Effect compartment
and within compartments
Incorporating
k1e
k12 k13
Second compartment Central compartment Third compartment
2 1 3
k21 V1 k31
k10
Elimination
Central compartment represents blood or plasma
Second compartment could represent the highly perfused tissues
Third compartment could represent the poorly perfused tissues
k21 k12 k31 k13 and k1e are intercompartmental distribution rate constants i.e. they describe the proportions of drug exchanged between compartments per unit time
k10 is the elimination rate constant from the central compartment
keo is the rate constant describing drug elimination from the effect site.
12. 6
Clinical benefits
The rapid onset and short duration of action of ‘Diprivan’ enable Numerous empirically-designed bolus or infusion administration
good control of the depth of anaesthesia and good quality of schemes have been reported for ‘Diprivan’. Infusion rates have been
recovery. adjusted manually within a typical range of 4 to 12 mg/kg/h.
The pharmacokinetic profile enables blood concentration – and
Quality of induction hence depth of anaesthesia – to respond rapidly to changes in the
Induction of anaesthesia with ‘Diprivan’ is characteristically smooth, infusion rate of ‘Diprivan’. When fixed-rate infusion of ‘Diprivan’
rapid and reliable. Induction time is related to the speed of injection. commences, there is a rapid increase in blood concentration
For instance, with a fixed dose of 2.5 mg/kg, mean induction time followed by a more gradual increase. A linear relationship between
was 30.8 seconds with an injection time of 20 seconds and 58.4 the infusion rate of ‘Diprivan’ and steady-state blood concentrations
seconds with an injection time of 80 seconds.10 The overall quality has been demonstrated; with continuous infusions of 3, 6 or
of induction was rated as good or adequate in about 90% of patients 9 mg/kg/h for at least 2 hours, blood concentrations were 2.1, 3.6
who received ‘Diprivan’ 2.0 mg/kg or 2.5 mg/kg.11 Patients over and 5.9 µg/ml.15
55 years of age may require lower doses of ‘Diprivan’. In practice, infusion rates of ‘Diprivan’ are titrated against the
The additive or synergistic hypnotic effects of ‘Diprivan’ with clinical response of the individual patient because of interpatient
benzodiazepines or opioids is well documented.1 variability as well as differences in the degree of surgical stimulation
There is interindividual variability with respect to plasma or and the use of supplementary analgesics.
blood concentration and response during induction with ‘Diprivan’.
The anaesthetic endpoint of loss of consciousness (loss of response to Quality of recovery
verbal or tactile stimuli) occurred in 50% of patients with plasma Extensive clinical experience has established that anaesthesia with
concentrations (Cp50 or EC50) ranging from 2.7 to 3.4 µg/ml.12–14 ‘Diprivan’ is characterised by a prompt, clear-headed recovery.
Lower plasma concentrations were required to achieve loss of All stages of recovery have been evaluated, especially in
eyelash reflex12 whereas higher plasma concentrations were required investigations of ‘Diprivan’ in the induction and maintenance of
to prevent movement on skin incision.14 anaesthesia for day-case surgery (see reviews1,16). Early recovery (or
emergence), as defined by time to eye-opening and orientation,
Quality of maintenance is rapid and predictable after ‘Diprivan’.17–20 Fast intermediate
Maintenance of anaesthesia with ‘Diprivan’ is characterised by recovery, including the early return of cognitive and psychomotor
smooth, easy control of the depth of anaesthesia and good function and early time to discharge,17–20 has been demonstrated
haemodynamic stability. ‘Diprivan’ has been used to maintain after ‘Diprivan’. Features of the late stage of recovery (i.e. complete
anaesthesia during a wide variety of surgical procedures ranging return to the preoperative state and resumption of normal activities)
from short procedures lasting only 10 minutes to major procedures have also been studied after ‘Diprivan’.
lasting several hours.
13. 7
Clinical benefits
Figure 2. Reduced risk of postoperative vomiting after anaesthesia with Figure 3. Quality of recovery after ‘Diprivan’ 22
‘Diprivan’ compared to inhalational agents 21
All Isoflurane Desflurane
inhalational (maintenance) or sevoflurane
agents (maintenance)
Excellent 60.9%
Excellent 58.0%
Reduction in risk of vomiting after ‘Diprivan’
1.0
(induction and maintenance)
2.3
2.0
Good 31.9%
6 studies Good 23.1%
p= 0.003
3.0
3.7 3.7 Poor 1.5% Poor 1.5%
Rating by Rating by
anaesthetists postanaesthesia
4.0 70 studies 42 studies Percentage of patients care unit
p <0.0001 p< 0.0001
(PACU) nurses
n =4,074 Percentage of patients
Meta-analyses of studies that recorded the incidence of vomiting (total of 70 studies Total population of 25,981 surgical patients (age range 18–80 years) and 1,819
comprising 4,074 patients). Log-odds ratios and confidence limits were calculated and anaesthetists (from 1,722 institutions in USA). Recovery information was missing from
presented in the paper together with the represented values for reduction in risk. 17.4% of data collection forms completed by anaesthetists and from 5.7% of forms
completed by PACU nurses.
The occurrence of adverse events such as postoperative nausea ‘Diprivan’ than after an inhalational agent (Figure 2); the difference
and vomiting (PONV) has a major influence on the quality of was evident (p < 0.0001) for adults (57 studies, 3.5-fold risk
recovery – and on the duration of postoperative stay. reduction) and for children (13 studies, 5.7-fold risk reduction).21
Importantly, there is a low incidence of PONV associated with Also, the risk of vomiting was significantly reduced after ‘Diprivan’
‘Diprivan’ anaesthesia.17–20 A recent meta-analysis 21 of randomised compared with isoflurane (Figure 2) or the newer agents, desflurane
controlled studies of anaesthetic agents showed that there was a or sevoflurane (Figure 2).21
2.7-fold reduction in the risk of nausea and/or vomiting for patients An American post-marketing survey 22 of over 25,000 patients
who were induced and maintained with ‘Diprivan’ compared with who received ‘Diprivan’ included a global evaluation by anaesthetists
those maintained with inhalational agents (p<0.0001). Patients were and nurses of patient recovery (Figure 3). Quality of recovery was
3.7 times less likely to vomit postoperatively after anaesthesia with rated as excellent or good for the vast majority of the patient
14. 8
‘Diprivan’
Figure 4. Most commonly reported adverse events associated with population (Figure 3). Anaesthetists were more likely to rate
administration of ‘Diprivan’22 recovery as poor when emergence from anaesthesia was delayed or
there was postoperative confusion.
Pain on injection 5.2%
Nurses were more likely to rate recovery as poor when nausea
Nausea and/or vomiting
and/or vomiting occurred or there was postoperative pain. Rating
1.9%
of recovery as poor by both anaesthetist and nurse was noted for
only 0.6% of patients.
Excitement 1.3%
The survey 22 also confirmed low frequencies of adverse events
Hypotension 1.1% (Figure 4) often associated with rating of recovery as poor; examples
included nausea and/or vomiting (1.9%), light or delayed anaesthesia
Bradycardia 0.4% (0.2%), postoperative confusion (0.2%), somnolence (0.2%) and
excitement (1.3%) associated with ‘Diprivan’.
Pain 0.3% The clinical and economic benefits resulting from the
favourable recovery profile of ‘Diprivan’ are summarised (Table 2)
Hypertension 0.3% with particular reference to anaesthesia for day-case surgery.
Measurements of blood concentrations during recovery after
Rash 0.2% ‘Diprivan’ infusion have demonstrated that patients awaken when
concentrations are in the region of 1 to 2 µg/ml.27,28
Confusion 0.2%
Coughing 0.2% Table 2. Clinical and economic benefits resulting from recovery profile
of ‘Diprivan’ for anaesthesia in day-case surgery
Somnolence 0.2%
Clinical benefits of ‘Diprivan’
Light or delayed
anaesthesia
0.2% q Short time to recovery17–20
q Low incidence of PONV 17–20
Tachycardia 0.1%
q Short time to discharge17–20
Laryngismus 0.1%
Economic benefits
Total with report
of adverse event
10.8% q Saves nursing time in the recovery room20,23,24
q Limits the need for anti-emetic therapy 25,26
5% 10% 15%
n = 25,891 Percentage of patients
q Allows patients an early return to work 24
15. 9
Target Controlled Infusion (TCI)
The basic rationale for Target Controlled Infusion (TCI)
of an intravenous anaesthetic agent is to enable the
anaesthetist to alter the depth of anaesthesia in as simple
a manner as using standard volatile anaesthetics delivered
via calibrated vaporizers. With TCI, induction and
maintenance are a continuous process with a single
agent unlike the separate use of an intravenous agent for
induction and an inhalational agent for maintenance.
A TCI system should improve both the convenience
of administration and ease of control of anaesthesia
compared with conventional infusion techniques.
This section reviews the scientific principles and
research background to TCI in anaesthesia.
16. 10
Development of concept and terminology
The concept of pharmacokinetic models with mathematical
equations to describe infusion schedules to provide a target
Key components
concentration in blood of an intravenous drug originated in 1968.29 Software and hardware are required to achieve and maintain a
By the early 1980s, a group in Bonn, Germany, had suggested and target blood concentration of an anaesthetic by balancing the rate
demonstrated that a computer-controlled infusion pump could Table 3. The key components of a TCI system and considerations
deliver complex infusion schedules of intravenous anaesthetic for commercial development
agents.30 Subsequently, numerous investigators in Europe and the
Key components – basic software and hardware
USA reported experimental systems linking computer software and
hardware to the operation of an infusion pump for delivery of q Pharmacokinetics – a validated model with specific
intravenous drugs to the patient. parameters for drug
q Algorithm(s) to control infusion rate
Acronyms q “Control unit” i.e. software and microprocessors for above
Researchers have referred to the basic concept of utilising a pharma- q Infusion pump
cokinetic model and microprocessor (= computer) to control an q “Communication” system between “control unit”
and infusion pump
infusion pump, by the following acronyms:
q User interface for input of patient data and
q CATIA – Computer Assisted Total Intravenous target blood concentration
Anaesthesia
Considerations for development of a commercial system
q TIAC – Titration of Intravenous Agents by Computer
q Standardisation of the pharmacokinetic model
q CACI – Computer Assisted Continuous Infusion for a particular drug
q CCIP – Computer Controlled Infusion Pump. q Validation of the system software and
production processes
The acronym TCI (Target Controlled Infusion) is now used q Safety mechanisms in the unlikely event of
as a broader term to describe the technique for the continuous malfunction of components
control of the concentration in blood or plasma of infused drug.31 q Integration of basic software and hardware with
TCI involves the use of a microprocessor to manage the pump. infusion pump to provide a reliable and portable unit
Instead of setting an infusion rate in terms of mg/kg/h, the q User interface to be as simple to operate as the controls
anaesthetist enters the following: of a vaporizer
q Convenient syringe presentation of drug
q Body weight of the patient
q Documentation (e.g. prescribing information, user guides)
q Age of the patient for drug and device
q Required blood concentration of the drug q Automatic recognition device for correct drug identification
and usage
(= target blood concentration in µg/ml).
17. 11
Development of concept and terminology
of infusion with the processes of distribution and elimination. The user interface should, ideally, be as simple to operate as the
This requires information about the pharmacokinetic properties controls of a vaporizer. Obviously, a suitable syringe presentation of
of the drug in appropriate patients. the drug with documentation such as amended prescribing
Software in the microprocessor incorporates a pharmacokinetic information and user guides for drug and pump are required for a
model and a specific set of parameters for the drug to be infused. commercial TCI system. Finally, an automatic recognition device
The microprocessor continuously calculates the variable infusion for identification of the correct drug and concentration would
rates required to achieve a predicted blood concentration. An provide an important safety feature.
algorithm controls the operation of the infusion pump so that
infusion rates are altered automatically to achieve this blood Defining TCI for anaesthesia
concentration. The TCI system maintains the blood concentration TCI is not a system for the complete computer control of
until a new target is set by the anaesthetist. anaesthesia. When using TCI, the anaesthetist adjusts the target
The choice of pharmacokinetic model and infusion control blood concentration of drug and titrates to clinical effect. A TCI
algorithm are major determinants of the performance of a TCI system is a convenient tool to assist the anaesthetist in adjusting
system. Different models and algorithms produce different actual the depth of anaesthesia. Control still rests with the anaesthetist,
blood concentrations even if the same target blood concentration who uses clinical signs or more sophisticated means of
is selected. monitoring. As such, a rigorous definition of TCI, as applied to
These key components of any TCI system in terms of software anaesthesia, is as follows:
and hardware are summarised (Table 3).
Considerations for commercial Definition of Target Controlled Infusion (TCI)
development When applied to anaesthesia,TCI is an infusion system which
allows the anaesthetist to select the target blood concentration
Aspects of safety, reliability and user convenience are foremost required for a particular effect, and then to control depth of
considerations for the development of a commercial TCI system anaesthesia by adjusting the requested target concentration.
(Table 3).
Standardisation of the amount of drug delivered at a particular
target setting (i.e. the pharmacokinetic model) for all systems used
with a given drug is an important requirement. The system
software and production processes must be validated. A basic safety
mechanism will shut the system down in the unlikely event of
malfunction of software or hardware. Integration of the basic
hardware and software with the infusion pump is important for a
commercial system; an integrated system should be more reliable
and portable than configurations used for research purposes.
18. 12
Benefits of TCI
Several potential benefits of TCI over manually controlled infusion Table 4. Benefits of TCI
(Table 4) have been summarised in authoritative reviews32,33 and
Convenience in use
textbooks.34,35 Benefits can be considered mainly in terms of
convenience in use and control of anaesthesia.32 Practical aspects
q Simple to operate
Convenience in use q Easy to titrate the level of anaesthesia
The simplicity of operation and ease of titration to anaesthetic effect q Displays calculated blood or plasma concentrations
with a TCI system mean that it can be likened to an “intravenous q Compensates for interrupted infusion
vaporizer”.36 q Avoids the need for time-consuming calculations
q Continuous process from induction through to maintenance
Simple to operate
With TCI, the anaesthetist simply sets the initial target blood Control of anaesthesia
concentration required for an intravenous drug in a similar way to Theoretical aspects
setting the percentage concentration of an inhalational agent with q Good control of depth of anaesthesia
a vaporizer. The target concentration is achieved and maintained q Gives stable anaesthesia
with no further intervention required by the user. q Improved control of cardiovascular and
respiratory parameters
Easy to titrate the level of anaesthesia
q Induction phase can be used to predict maintenance effects
Titration of the target concentration and therefore the depth of
anaesthesia is rapid and predictable with a TCI system. Setting a new Compiled from references 32–35
target concentration produces a proportional change in the depth of
anaesthesia. This is unlike the situation with inhalational anaesthetics a constant infusion rate produces fluctuations in blood concentration
where “overpressure” is often used to titrate rapidly to deeper levels in relation to distribution and elimination of drug. Also, manual
of anaesthesia. control with variable infusion rates can often require calculations for
TCI facilitates the direct transfer of fundamental skills learnt alterations. Supplementary bolus doses may be needed to increase
with inhalational agents. Target concentration is readily increased the depth of anaesthesia.
in anticipation of stimulating events (e.g. placement of laryngeal
Displays calculated blood concentration
mask airway or surgical incision). Similarly, target concentration
can be readily decreased to tailor the level of anaesthesia needed With TCI, there is a constantly changing display of calculated (or
towards the end of surgery. predicted) blood concentration. The system may also provide
A TCI system is easier to operate than a manually controlled information on the time required to reach the desired target
infusion pump. The required target value can be achieved accurately concentration. This advisory information from a TCI system, in
and rapidly – and then maintained. In contrast, manual control with conjunction with clinical signs, enables the anaesthetist to assess
19. 13
Benefits of TCI
progress and whether further changes are required i.e. the target concentration. With manually controlled infusion, such a
anaesthetist “knows where he/she is up to.” procedure requires skill and experience to manage with a similar
degree of precision.
Displays calculated effect-site concentration
Avoids the need for time-consuming calculations
Some systems have the facility to display the propofol concentration
calculated to exist at the effect-site in the brain. This concentration Infusion rates do not need to be calculated when using a TCI
tends to lag behind the blood concentration when the target system. The anaesthetist simply selects a target blood concentration.
concentration is increased, and provides an indication of the degree The system makes continuous calculations and controls the rate of
of equilibration which exists at a given time between blood and brain drug infusion so as to achieve and maintain the requested target
concentrations of propofol. concentration – and the desired level of anaesthesia. With manual
Pharmacodynamic effects are likely to be more closely related control of an infusion pump, calculations are needed for the initial
to effect-site concentrations but guidance in ‘Diprivan’ prescribing infusion rate and subsequent adjustments so as to maintain a stable
information on setting of target concentration refers only to target level of anaesthesia.
blood concentrations. However, the provision of advisory Potential benefits that arise from the above aspects of ease of
information on effect-site concentration should assist the use of a TCI system include:
anaesthetist in making more rational adjustments to the blood target q TCI might allow the anaesthetist more time to focus on
setting e.g. delaying an increase in target if the effect-site monitoring the patient
concentration indicates only partial equilibration. q TCI might avoid errors in dosage sometimes associated
with manual control of complex infusion regimens.
Predicts patient waking time
Some TCI systems have the facility to display predictive information Control of anaesthesia
about the time required to achieve a lower calculated concentration There are some theoretical or potential clinical benefits of TCI
if the infusion were to be stopped (decrement time). The anaesthetist over conventional intravenous drug administration techniques that
can then easily modify drug administration to optimise the speed of stem from the predictability of anaesthetic effects during induction
recovery. The decrement time displayed is influenced by the and maintenance.
expected waking concentration which can be adjusted by the
anaesthetist. Good control of depth of anaesthesia
TCI may assist precise control of the depth of anaesthesia by
Compensates for interrupted infusion allowing the anaesthetist to make rapid and predictable changes
When an infusion is interrupted (e.g. for a change of syringe), a TCI simply by setting a new target blood concentration. It is easy to
system may make automatic compensation. When infusion stops, the make proportional changes in target concentration so that the level
system continues to predict the blood concentration. When infusion of anaesthesia can be readily titrated as necessary to suit individual
restarts, the rate is adjusted automatically to maintain the desired patients and varying degrees of stimulation.
20. 14
Target Controlled Infusion (TCI)
The initial target concentration required to induce anaesthesia maintenance of anaesthesia, blood concentrations could rise higher
is selected according to age, ASA status, premedication and or fall lower than intended with manual alteration of the rate of drug
supplementary analgesic administration. Response to the initial target administration; there could be a corresponding loss of control of
concentration may be used as a guide to subsequent requirements, haemodynamic variables. A TCI system provides more predictable
including during the maintenance phase. blood concentrations. There is automatic reduction of drug
TCI allows the anaesthetist to make small (e.g. 0.1 µg/ml) as administration when the predicted concentration is reached. Manual
well as large changes (e.g. 1 µg/ml) to target concentration at any administration of supplementary bolus doses is not required with
time. Stimulating events (e.g. surgical incision) may be anticipated by TCI. Overall, a TCI technique may provide smoother control of
increasing the target concentration. Decreases in target concentrations anaesthetic, haemodynamic and respiratory effects than manually
may be required in response to events such as a fall in blood pressure. adjusted administration techniques.
Target concentrations can also be reduced as the operation progresses
in anticipation of the end of surgery. Other benefits
When an intravenous anaesthetic agent is administered by a
Stability of anaesthesia TCI technique, induction and maintenance can be viewed as a
Theoretically, a more stable blood concentration of drug – and continuous process.
more precise control of the depth of anaesthesia – may be obtained TCI facilitates TIVA. There is the general advantage with
with TCI than with manual methods of administration. The TIVA of avoiding the use of, and therefore occupational exposure
response of the patient to surgical stimulation may be countered to, inhalational agents.
rapidly and in a well-controlled manner with TCI. As mentioned, A TCI system makes the administration of an intravenous agent,
the anaesthetist titrates to effect. The facility to make small especially for maintenance, analogous to the use of a vaporizer.
increments and decrements to target concentration is useful should The features of the syringe pumps and microprocessors that
the anaesthetist have to “fine tune” the depth of anaesthesia in form part of a TCI system for anaesthesia may confer additional
“difficult” patients e.g. those with respiratory or cardiovascular advantages such as:
disease. q Portability
Control of cardiovascular and respiratory parameters q Data storage and retrieval capability
q Creation of documentary record at the time of the
The careful control of blood concentrations of drug with TCI could,
anaesthetic procedure (e.g. for clinical audit).
in theory, improve haemodynamic and/or respiratory stability – and
help to avoid dose-dependent events such as apnoea or hypotension. The general benefits of TCI as outlined in this section are
Conventional bolus administration of an induction dose of an obtainable with many prototype TCI systems. ‘Diprifusor’ takes
intravenous anaesthetic agent may produce an “overshoot” of blood these benefits and adds features such as an improved user interface
concentration; with some agents, there is a high attendant risk of and improved portability, details of which are given in the next
apnoea or an undue reduction in blood pressure. Similarly, during section.
23. 17
‘Diprifusor’ TCI – practical aspects
‘Diprifusor’ (TCI Software/Subsystem/System for
‘Diprivan’) is the first commercially available TCI system
and is incorporated in syringe pumps from leading
manufacturers. This section summarises practical aspects
including user requirements.
The term ‘Diprifusor’ is used when referring to the
infusion system whereas ‘Diprifusor’ TCI is used to
describe the technique of anaesthetising a patient with
‘Diprivan’ using a ‘Diprifusor’ system (see also Glossary
on page 58). ‘Diprifusor’ TCI is only indicated for
anaesthesia in adult patients (see also Prescribing
Information for ‘Diprivan’).
24. 18
General requirements for use of
‘Diprifusor’ TCI
The basic requirements for anaesthetising a patient with ‘Diprifusor’
TCI are:
q Documentation – information from the pump manufacturer
(e.g. Instruction Manual) and from AstraZeneca
(current Prescribing Information for ‘Diprivan’ and Guide
for Anaesthetists on administration by ‘Diprifusor’ TCI)
q Drug – ‘Diprivan’ Pre-Filled Syringe (PFS) with recognition
tag
q Delivery system – commercially-available syringe pump
incorporating ‘Diprifusor’.
25. 19
‘Diprivan’ Pre-Filled Syringe (PFS)
A range of Pre-Filled Syringe (PFS) presentations of ‘Diprivan’ has Regarding pack sizes, most markets will have 1 x ‘Diprivan’
been developed. Your local AstraZeneca representative or office PFS in a blister tray packed into an outer carton. Packaging
will be pleased to advise on available presentations, whether includes statements that the ‘Diprivan’ PFS can be used for
‘Diprivan’ 1% or 2% and syringe sizes. ‘Diprifusor’ TCI.
For administration by TCI, a ‘Diprivan’ PFS first needs to be The blister tray (Figure 5) contains the following components:
assembled before loading into a syringe pump that incorporates
q PFS (glass barrel containing sterile drug; rubber stopper
‘Diprifusor’.
and rubber plunger; colour-coded crimp and “flip-off”
The ‘Diprivan’ PFS can be used for the following methods of
plastic seal)
administration:
q Finger grip (fitted into base of glass barrel, incorporates a
q TCI with a syringe pump that incorporates ‘Diprifusor’ recognition tag*)
q “Manual” control of infusion with compatible syringe
pumps i.e. appropriate setting of syringe size as for 50/60 ml q Plastic plunger rod (for attachment to the screw threads of
B-D Plastipak the rubber plunger)
q Hand-held. q Luer connector (as a separate sterile unit).
Figure 5. ‘Diprivan’ PFS components in blister tray
Plastic plunger rod (for attachment to the
screw threads of the rubber plunger)
Luer connector
(as a separate
sterile unit)
Finger grip
(fitted into base of
glass barrel,
incorporates
a recognition tag*)
Plastic Colour-coded Rubber Glass barrel Rubber
“flip-off” aluminium crimp stopper containing sterile drug plunger
seal (blue = 1%, red = 2%)
26. 20
‘Diprifusor’ TCI – practical aspects
when the PFS has been loaded correctly. Magnetic resonance
Assembly and aseptic precautions “signals” are generated by the tag. An aerial (Figure 6) in the syringe
PFS components need to be assembled before use. Detailed assembly pump detects these signals and relays them to the ‘Diprifusor’ TCI
instructions are on the back of the carton and with the blister tray. All Subsystem.
presentations of ‘Diprivan’ support microbial growth and are for The electronics and software in the ‘Diprifusor’ TCI Subsystem
single use in an individual patient. The exterior of the syringe and the “read” these “signals” and ensure that:
plunger are not sterile. Asepsis must be maintained during assembly –
and subsequent use. q The syringe pump will only operate in ‘Diprifusor’ TCI
The standard aseptic precautions for ‘Diprivan’ PFS are as mode with a tagged ‘Diprivan’ PFS
follows: q The ‘Diprifusor’ TCI Software recognises whether a 1%
or 2% ‘Diprivan’ PFS has been loaded.
q Single use in an individual patient – the PFS is NOT A
MULTIDOSE CONTAINER There are two consequences for safe operation:
q Maintain asepsis for both ‘Diprivan’ and infusion equipment
q ‘Diprivan’ is the only drug that is infused when the syringe
q Discard unused drug. pump is in ‘Diprifusor’ TCI mode
The maintenance of asepsis starts with alcohol swabbing or q The automatic confirmation of concentration means that
spraying of the rubber stopper after removal of the “flip-off” plastic the correct infusion pattern – and target concentration –
seal. is obtained irrespective of whether a 1% or 2% ‘Diprivan’
There is a built-in safety feature with ‘Diprifusor’ to help prevent PFS is loaded.
refilling and multiple-patient use of the ‘Diprivan’ PFS. A detailed A third feature enhances patient safety relating to aseptic
description follows. precautions. When the contents of a ‘Diprivan’ PFS have been
infused, the recognition tag is erased. This helps prevent any
Recognition tag in finger grip refilling and reuse of that syringe in TCI mode whether in the same
The recognition tag* (“electronic marker”) in the finger grip of a or another patient. The user can, of course, load another tagged
‘Diprivan’ PFS provides important safety features for correct drug ‘Diprivan’ PFS. (The syringe pump displays instructions about
identification and usage.43 loading a new ‘Diprivan’ PFS and ‘Diprifusor’ provides automatic
The tag is an encoded capsule that is visible on one side of the compensation for the short interruption.)
finger grip. To load a ‘Diprivan’ PFS into a syringe pump that
incorporates ‘Diprifusor’, the tagged side of the finger grip is inserted * Programmable Magnetic Resonance (PMR) tag in the finger grip of a ‘Diprivan’
into the slot (syringe “ear groove”) and rotated. The display indicates Pre-Filled Syringe: this technology is licensed from Scientific Generics Limited.
27. 21
‘Diprivan’ Pre-Filled Syringe (PFS)
Figure 6. ‘Diprifusor’ TCI System
Finger grip
Full ‘Diprivan’ PFS Tag = PMR
is loaded correctly (Programmable Magnetic
Resonance)*
Aerial
‘Diprifusor’
TCI Subsystem Pump
Recognition software/electronics
software
‘Diprifusor’ TCI Software/
2 microprocessors
Pump hardware
Safety features of recognition capability
q Operates in ‘Diprifusor’ TCI mode only with tagged
‘Diprivan’ PFS – no other drugs
q Confirms ‘Diprivan’ concentration (1% or 2%) for correct
infusion at requested target concentration
q Erases tag when PFS is nearly empty and prevents
refilling/reuse
‘Diprifusor’ TCI Software and microprocessors
q Control unit for syringe pump when in ‘Diprifusor’ TCI mode
* Programmable Magnetic Resonance (PMR) tag in the finger grip of a ‘Diprivan’ Pre-Filled Syringe: this technology is
licensed from Scientific Generics Limited.
30. 24
Syringe pumps incorporating ‘Diprifusor’
Graseby Medical (Watford, UK), Vial Médical (Fresenius Vial,
Brézins, France) and ALARIS Medical Systems (Basingstoke, UK)
General principles
The following operations are required for infusion of ‘Diprivan’
are the manufacturers of the first commercial infusion systems to using a pump that incorporates ‘Diprifusor’:
incorporate ‘Diprifusor’.
q Correct loading of tagged ‘Diprivan’ PFS
Graseby has developed the Graseby 3500, a new model based
q Priming of the infusion line with ‘Diprivan’ (i.e. expelling air
on the established Graseby 3400 Anaesthesia Syringe Pump. Vial
from the infusion line while disconnected from the patient).
Médical has developed the Master TCI as a “sleeve” attachment to
Priming should be done with the BOLUS or PURGE
upgrade the established Pilot Anaesthesia syringe pump. ALARIS button of the pump to take up any piston “backlash”
has developed the new IVAC TIVA TCI syringe pump. These q Selecting or ensuring that the pump is in ‘Diprifusor’ TCI
pumps have a clearly visible “label” indicating that they incorporate mode
‘Diprifusor’ – with the ‘Diprifusor’ brand name and logotype q Checking that the pump recognises ‘Diprivan’ 1% or 2%
(stylized D with arrow logo). Performance standards for drug and prompts the necessary user inputs
delivery are identical. q Inputting and entering
Details of the availability, features and operation of these – age of patient in years
pumps can be obtained from the local representative or office of – body weight of patient in kilograms (kg)
each manufacturer. The following brief review serves to illustrate – initial target concentration in micrograms per millilitre
aspects of the user interface relevant to the administration of of blood/plasma (µg/ml)
‘Diprivan’ by TCI. q Starting infusion.
Figure 8. Main components of a ‘Diprifusor’ TCI system
Anaesthetist selects
and inputs target Patient
blood concentration
Anaesthetist inputs ‘Diprifusor’ TCI Subsystem
Infusion pump incorporating
patient data Microprocessor
‘Diprifusor’
(age, body weight) + pharmakokinetic program
Adapted from reference 32.
31. 25
Syringe pumps incorporating ‘Diprifusor’
In practice, the start-up procedures are much quicker and easier ‘Diprifusor’ TCI is only indicated for the induction and
than implied by the above list. The actual sequences, displays, maintenance of anaesthesia in adult patients.
prompts and mode of input differ with the three pumps. But they
are all “user friendly” and documented fully in the manual provided Main components
by the manufacturer. The main components of a ‘Diprifusor’ TCI system, the data inputs
Current users of the relevant anaesthesia pumps will readily and interactions between anaesthetist and patient are summarised
understand operation in ‘Diprifusor’ TCI mode. (Figure 8).
The anaesthetist enters patient data and selects the target blood
Patient data concentration.
The pumps will only accept patient data within these limits: Brief descriptions follow on the commercially available infusion
q Age 16–100 years systems with the emphasis on input of patient data and of target
blood concentration. Each pump can also be used in manual mode.
q Body weight 30–150 kg
The manufacturer’s manual (Instruction Manual, Operator’s Guide
q Target blood concentration 0.1–15 µg/ml (confirmation or Directions for Use) should be consulted for details of operation.
by user required for target greater than 10 µg/ml). The main features of each system are summarised in Table 6.
Table 6. Features of commercial syringe pumps that incorporate ‘Diprifusor’
Feature Graseby 3500 Vial Médical Master TCI ALARIS IVAC TIVA TCI
Design New model based on 3400 “Sleeve” attachment to upgrade New model based on ALARIS IVAC TIVA
Pilot Anaesthesia pump
Input/entry of patient data (age, weight) Numeric keypad/press ENTER button Dial value/press knob Chevron and soft keys
Set initial target concentration Numeric keypad/press ENTER button Dial value/press knob Chevron and soft keys
Small adjustment to target Soft keys Dial value/press knob Single chevron keys/press START
Large adjustment to target Input new value with numeric keypad/ Dial value/press knob Double chevron keys/press START
press START button
Screen display of target and calculated concentration Numerical Graphical and numerical Graphical and numerical
Display of effect-site concentration* Yes Yes Yes
Display of decrement time* Yes Yes Yes
Display of infusion rate and volume Yes Yes Yes
PC/printer interface to down-load data Yes Yes Yes
and create records
Comprehensive range of alarms Yes Yes Yes
*Access, display and terminology differ between pumps and these facilities may not be available on some versions (see manufacturer’s manual)
All features and specifications are subject to upgrades and other changes; the manufacturer should be consulted for details.
32. 26
‘Diprifusor’ TCI – practical aspects
Graseby 3500 Anaesthesia Syringe Pump Small alterations (minimum 0.1 µg/ml) to target concentration
are made by pressing the up ( ) or down ( ) soft keys found
The new 3500 model incorporating ‘Diprifusor’ is shown below below the display. For large alterations, the numeric keys/START
(Figure 9). The numeric keypad is used to input the age and weight button are used to input and confirm the new target setting and
of the patient as well as the initial target concentration. (The user continue infusion with the new target.
does not have to enter any units.) After each input, an ENTER soft When the pump is infusing, pressing the INFO soft key gives
key is pressed. Pressing the START button will commence the access to the following displays:
infusion. q Effect-site concentration (calculated)
The display (Figure 10) during infusion highlights the
q Time to target (calculated)
target concentration and the calculated concentration. The
default setting of target concentration is 4 µg/ml. The current q Time to lower target (calculated decrement time)
infusion rate also appears. The TOTAL soft key allows access to q Patient details (inputted age and weight).
the current total amount of infusion.
Figure 9. Graseby 3500 pump incorporating ‘Diprifusor’ Figure 10. Display panel of Graseby 3500 pump during ‘Diprifusor’ TCI
Liquid Crystal Display (LCD)
Display panel CALCULATED concentration TARGET
(includes target and START STOP concentration
calculated concentrations) button button
TCI
status
TARGET:
4.0 indicator
CALCULATED
2.8 µg/ml
TCI (INFUSION RATE 1200ML/H)
status INFO TOTAL
indicator
Small increment Small decrement Access INFO on Access TOTAL
effect-site (brain) amount of
4 soft keys 12 numeric keys Power Power concentration, time to target ‘Diprivan’ infused
(input of age, weight, ON OFF
initial target) TCI status indicators , the word CALCULATED and
symbol blink during infusion
Consult Instruction Manual for details of display and operation. Consult Instruction Manual for details of display and operation.
33. 27
Syringe pumps incorporating ‘Diprifusor’
Serial linkage of the Graseby 3500 (via an RS232 interface) to Figure 11a. Master TCI module incorporating ‘Diprifusor’ for
Vial Médical Pilot Anaesthesia syringe pump
a Personal Computer (PC) enables down-loading of data and
creation of a record of the anaesthetic procedure. (Please contact Existing Pilot Anaesthesia syringe pump
Graseby for the computer protocol; such facilities are features of
the pump and not of ‘Diprifusor’.)
Alarm messages are similar to those during manual control of
infusion (see Instruction Manual).
Numerous display languages are available and can be
individually selected.
Vial Médical Master TCI unit for
+
Master TCI module
Pilot Anaesthesia syringe pump
A Pilot Anaesthesia syringe pump can be upgraded to capability
for ‘Diprifusor’ by adding a Master TCI unit (Figure 11).
A control knob is used to dial up the following inputs:
q Age of patient
q Weight of patient
q Target concentration.
The user does not have to key in any values; the knob is
turned to select the required value from a full listing on the display
= Knob to dial inputs
‘Diprifusor’ System (age, weight,
screen. Simply pressing the knob enters the value. The infusion target concentration)
begins when the START button is pressed. To set any new target, Press knob to enter
Figure 11b
START STOP
Display panel button button
Consult Operator’s Guide for details of display and operation.
34. 28
‘Diprifusor’ TCI – practical aspects
the user dials up (i.e. turns the knob) to indicate the new value and Information nor is it supported by clinical trials data for the
then presses the knob. administration of ‘Diprivan’ by ‘Diprifusor’ TCI.
The screen becomes a graphical display (Figure 12) of calculated The Master TCI has data storage (15,000 events) and retrieval
concentration against time with the target concentration clearly capability. Patient initials or number can be assigned as an
marked. The curve shows where calculated concentrations are in individual identifier. Data can be displayed on screen or down-
relation to the target. The screen can be changed to a listing of loaded to a PC to create documentary records including the curve
numerical values for target, calculated, infused dosage, duration and of calculated concentrations against time. This facility is a feature of
flowrate. the pump and not of ‘Diprifusor’.
The main display includes calculated decrement time (based on Alarm messages are similar to those during manual control of
an “awakening” concentration selected by the anaesthetist) and a infusion with a Pilot syringe pump (see Operator’s Guides for
graph of calculated effect-site concentration. Master TCI/Pilot).
The Master TCI offers a choice of induction mode. The initial
target concentration can be achieved as quickly as possible based on
‘Diprifusor’ or achieved gradually according to a selected induction
ALARIS IVAC TIVA TCI Syringe Pump
time of between 30 seconds and 10 minutes. The ALARIS IVAC TIVA TCI is shown opposite in Figure 13.
The gradual mode of induction is not a feature of ‘Diprifusor’ The chevron and soft keys are used to input the age and weight
but of the pump. This option is not included in Prescribing of the patient as well as the initial target concentration. After
confirmation, the main display is shown and pressing START
Figure 12. Display panel of Vial Médical Master TCI during will commence TCI. All the information relevant to TCI is
‘Diprifusor’ TCI shown on the main display.
Graphical Liquid Crystal Display (LCD) Target concentration and the continuously changing
Concentration Decrement time Target calculated concentration are displayed numerically (Figure 14).
µg/ml (to predict time concentration In addition, a graphical trend is displayed of the calculated
of awakening)
concentration which builds up as the infusion proceeds. This
trend graph depicts the concentration over the last 30 minutes,
10 min 2 µg/ml
2 hours or 8 hours. The calculated effect-site concentration is
Effect-site 5
shown as an icon in the top right hand corner and below this is
concentration
an optional display of estimate time to a preset lower
concentration (decrement time). The volume infused and
0 h 00 (324 ml/h) 35 min infusion rate of ‘Diprivan’ are also displayed.
The target concentration may be titrated using the chevron
keys and START is pressed to confirm the new target. The
Time (minutes/hours) Current infusion rate Calculated concentration single chevron keys are used to make small changes
Consult Operator’s Guide for details of display and operation.
(0.1 µg/ml), and the double chevron keys used to make larger
35. 29
Syringe pumps incorporating ‘Diprifusor’
changes (1.0 µg/ml) to the target concentration. Figure 13. ALARIS IVAC TIVA TCI syringe pump incorporating ‘Diprifusor’
The ALARIS IVAC TIVA TCI has an event log, including START Main display OPTIONS
patient details, that can be reviewed on-screen and from which button (LCD) button
(features)
data can be retrieved via an RS232 interface.
Alarm messages are similar to those during manual control
of infusion with an ALARIS IVAC TIVA syringe pump. STOP
button
For further details of the ALARIS IVAC TIVA TCI
operation, please refer to the manufacturer’s Directions For Use.
Chevron keys Soft keys ON/OFF button
(input of age, weight, (prompts on (pump switch)
target concentration) main display)
Consult Directions for Use for details of display and operation.
Figure 14. ALARIS IVAC TIVA TCI panel and main display during ‘Diprifusor’ TCI
Calculated Pump Volume of Effect-site (brain) concentration
concentration status ‘Diprivan’ infused and estimate time
INFUSING 7.5ml 3.0µg/ml
0:03:03
4.0µg/ml
4.0µg/ml
Target + ADJUST - 37.0ml/h
0h:30m
concentration
Chevron keys for increment/decrement Trend graph of
calculated concentration
Consult Directions for Use for details of display and operation.