In title 12, 22, 11 are in subscript. / Thesis (PhD)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: The aim of this study was to test a synthetic protein-free surfactant preparation, LPM-l, with the same chemical composition as commercially available Exosurf (Glaxo Wellcome), but containing in addition, a sugar, trehalose (TRE). Towards this end, a study was designed to firstly test the hypothesis that the true difference in acute physiological effects between a mixture of oppe, tyloxapol, hexadecanol and trehalose (LPM-l), and Exosurf, (Oppe, tyloxapol and hexadecanol) is zero, in a surfactantdeficient animal model. A second study addressed the physiological effects of oppe, hexadecanol, tyloxapol and trehalose (LPM-l) compared to treatment with trehalose (TRE) or saline, in order to determine (1) the contribution of TRE to the mixture of oppe, hexadecanol and tyloxapol, and (2) to assess the effect of the LPM-l surfactant replacement on the epithelial lining fluid composition by means of analysing bronchoalveolar lavage fluid. Thirdly, the effects of TRE and / or calcium were studied on the surface properties of oppe suspensions, by in vitro analysis using the ring detachment method of Du Nouy The in vivo research comprised of two studies, performed in randomised controlled fashion. In the first study, 24 New Zealand White adult rabbits were randomised into 4 groups, while in the second study, 15 animals were randomised into 3 groups. In the first in vivo study, three synthetic surfactants, LPM-l, Exosurf and LPM-2, and a saline group were tested. LPM-l is a new formulation that consists ofa mixture of Df'PC, TRE, hexadecanol and tyloxapol. LPM-2 is a formulation with a composition equivalent to that of commercially available Exosurf, prepared on site. In both studies animals were subjected to repeated lavage with large volumes of warm saline (25 ml/kg) in order to establish surfactant deficiency and acute lung injury. Five minutes after the last lavage, vehicle, i.e. surfactants LPM-l, Exosurf, or LPM-2, or saline, in the first in vivo study, and LPM-l, TRE or saline in the second in vivo study, was instilled, and the course of the animals followed over the next 3 hours. Ventilator settings were standardized before and after lavage. The effects of surfactant treatment on gas exchange (arterial Pa02, oxygenation index (Ol), arterial-alveolar oxygen (a/A) ratio), percentage calculated shunt, and total dynamic respiratory compliance (CRSdyn), and histopathological changes were compared with changes in saline treated controls. Arterial blood gases in 100% oxygen and CRSdynwere measured before and after lavage, at 15 minute intervals for the first 30 min, then at 60, 90, 120, and 180 min after vehicle instillation. Oxygenation improved to a similar extent after LPM-l and Exosurf instillation, surpassing that of LPM-2 or saline. Overall, intratracheal instillation of both Exosurf and LPM-l, rapidly improved the gas exchange and reduced the intrapulmonary shunt, but did not restore the lung to its pre-lavage condition. From the 2nd in vivo study it was evident that trehalose-only, was inefficient as a lung surfactant, failing to improve oxygenation indices or the calculated percentage shunt, or influencing respiratory compliance. The addition of the sugar, trehalose (TRE), to the on-site 'Exosurf mixture (LPM-2) brought the activity of the resultant LPM-l to the same level as that of commercial Exosurf, but failed to raise the activity above that of Exosurf. These physiological improvements were sustained for up to 3 hours. Saline-treated animals had no improvement in gas exchange despite management with variable PIP (to maintain a tidal volume of -1 0 ml / kg) and constant PEEP of 5 cm H20. In-vitro results, obtained by the Ou Nouy tensiometer, showed higher mean ordinate surface tension values for the OPPC-only and DPPC + TRE mixtures, and the slopes of their respective graphs smaller in magnitude than those of the other formulations, suggesting that these formulations had less surface tension-lowering capability than the other surfactants. At 20°C (20 mg / ml DPPC-surfactants) the mean ordinate values of OPPC and OPPC + TRE, 70.13 and 69.47 dyne / cm, respectively, were not significantly different from each other. The mean ordinate values of LPM-l and the formulation containing OPPC + TRE + tyloxapol + CaCh were lower, but similar, as were the values of LPM-2 (on-site Exosurf) and LPM-2 + CaCho Thus, three internally homogeneous subgroups could be identified which differed significantly, namely: DPPC and DPPC + TRE, LPM-2 and LPM-2 + CaCh, and DPPC + TRE + tyloxapol + CaCh and LPM-l. Similar conclusions apply to the ordinate values of the surfactants at 37°C, and to the mean slope values at 20°C, with the exception that the subgroups, LPM-2 and LPM-2 + CaCh, and LPM-l and OPPC + TRE + tyloxapol + CaCh are not so clearly separated. A similar analysis of mean slope values was performed. Here too a significant difference between substances was found, OPPC alone or in combination with TRE, again being significantly different from the other surfactants. The most prominent light microscopy findings of the lungs of animals included general lymphatic dilatation, congestion and lung polymorphonuclear infiltration, with no difference between study groups. Hyaline membranes were present in all surfactant groups, but significantly more so in the saline treated group. In the first in vivo study, the presence of neutrophils in the lung interstitiwn as well as alveoli, was a common finding in all of the study groups towards the end of the study protocol. A significant increase in the BAL-fluid neutrophil count occurred in all animals, concurrent with a significant decrease in the BAL macrophage count. No significant change occurred in the peripheral neutrophil count during the 3-hour study, suggesting recruitment of neutrophils from storage pools. Treatment with synthetic surfactant (LPM -1) did not have a significant effect on modifying the inflammatory response, since there was no significant difference in the BAL-derived cell counts between the LPM-1 and -saline groups. Epithelial damage was a consistent finding in all groups. The damage was more evident by electron microscopy examination and included hydropic changes, most readily observed in the mitochondria. The airspaces of study subjects showed the presence of oedema fluid. This luminal oedema appeared to be more prominent in the control group and LPM-2 (on site 'Exosurf') group. Organellar debris, probably originating from lysis of epithelial cells, was present, despite treatment with synthetic surfactant. The electron microscopical appearance of the epithelial-lined substance ("hyaline membranes") in the present study showed a marked variability within groups as well as within the same case. The majority of cases showed a mix of membrane types with both granular and fibrillar materials present within the same membrane. In some cases there were layering of the membranes into distinct bands. The instillation of LPM-l resulted in the formation of a slightly different type of epithelial lining fluid after lavage, when compared to the prelavage composition. The most pronounced changes occurred within the fatty acids, whilst the phosphatidylcholine values remained unchanged. Palmitic acid concentrations (C16:0) increased significantly, suggesting enrichment of the epithelial lining fluid after instillation of LPM-l. This increase in C16:0 was concurrent with significant decreases in the percentage C16:1, C18:0, and C18:2. In contrast to previous studies, we describe higher levels for phosphatidyldimethylethanolarnine (PEA). An explanation may be that the lipid identified as PEA, was in fact partly phosphatidylglycerol (PG)-a lipid whose accurate identification was precluded for technical reasons. After surfactant instillation, the PC/SM ratio, a reflection of the lecithin / sphingomyelin (LIS), decreased significantly in the TRE-group between the first and final lavage, but remained statistically unchanged in the animals treated with LPM-l or saline. The change in ratio was mainly accounted for by a decrease in BAL-fluid PC content together with a rise in SM content. A poor correlation existed between the BAL-derived PC/SM ratio and indices reflecting oxygenation status (a/A ratio, Ol), as well as the CRSdynat the time of the final lavage. In conclusion, the primary hypothesis was accepted, LPM-l performed similarly to Exosurf in vivo, improving oxygenation, but not CRSdyn.None was clearly superior to the other. Some questions remain. The reason why LPM-l (LPM-2 + TRE) did not behave in a superior manner, in vivo, to Exosurf, is partly unclear. This finding was somewhat surprising since the chemical composition of Exosurf and LPM-2 did not differ, and the addition of TRE to LPM-2 (on-site Exosurf), did improve the in vivo activity of the resultant LPM-l, above that of LPM-2. A possible explanation for observed differences in performance include methodological issues, i.e. the preparation of the on-site formulations, especially that of LPM-2 (on-site Exosurf), may differ from the way in which true commercial Exosurf is prepared. / AFRIKAANSE OPSOMMING: Die doel van die studie was om 'n sintetiese proteïn vrye surfaktant te ontwikkel en die produk te vergelyk met 'n kunsmatige surfaktant reeds in kliniese gebruik. Die bekende uit die literatuur en die onbekende van die produk wat evalueer sou word, lei op tot die samestelling van die nul hipotese van die PhD naamlik dat geen verskil in longfunksie sou gewys word tussen die toetsproduk en reeds gebruikte kommersiële surfaktant nie. Die hipotese was dat 'n suiker (trehalose), in kombinasie met Dipalmitoiel fosfatidielcholine (DPPC), gaswisseling en longfunksies sal verbeter vir 'n long met 'n lae surfaktant konsentrasie. Vir die studie is jong volwasse wit New Zealand konyne gebruik en is hulle met 'n gestandaardiseerde en menslike manier gebruik in eksperimentele werk. Die diere is onder intraveneuse narkose geplaas en verskillende kardiovaskulêre en pulmonologiese aspekte is gemeet. Die long surfaktant is uitgewas deur middel van fisiologiese soutoplossing wat tot liggaam temperatuur verhit is en daarna is die diere prospektief gerandomiseer tot eksperimentele groepe. Met vooraf bepaalde tydsintervalle is die fisiologiese metings herhaal en was die metings toegespits daarop om longmeganiese funksie en gasoordrag vermoë te evalueer. Lig mikroskopiese en elektron mikroskopiese studies is ook op die longe gedoen en verder is brongoalveolêre vloeistof ook ontleed. Die groepe met ondersoek was: I. oppe, heksadekanol, tyloxapol en trehalose (LPM-I). 2. oppe, heksadekanol, tyloxapol (LPM-2 :. LPM-I sonder trehalose). Hierdie is 'n proteïnvrye surfaktant plaaslik berei ( dieselfde samestelling as Exosurf). 3. Exosurf®. (Kommersiële preperaat reeds in gebruik). Hierdie is 'n proteïnvrye sintetiese surfaktant. 4. Trehalose, 'n non-reduserende disakklaried van glukose. Addisioneel is daar ook in vitro studies gedoen waann die oppervlakte spanmngs aktiwiteite van die verskillende surfaktant oplossings vergelyk is. Die statistiese analise is gedoen in samewerking met Prof. J. Maritz wat 'n unieke metode ontwikkel en gepubliseer het om herhalende veranderlikes op 'n statisties verantwoordbare manier te ontleed. In die eerste van die studies, is LPM-I, Exosurf®, fisiologiese soutoplossing en 'n plaaslik bereide "Exosurf" (LPM-2), met 'n chemiese samestelling identies aan dié van kommersiële Exosurf®, evalueer. In 'n tweede studie is die fisologiese effekte van LPM-I vergelyk met trehalose of fisiologiese soutoplossing om die volgende te ondersoek: 1) Die bydrae van trehalose tot 'n mengsel van oppe, heksadekanol en tyloxapol (LPM-2). 2) Die gevolg van LPM-l surfaktant toediening op die konyn se brongo-alveolêre vloeistof samestelling. 'n Derde, in vitro studie, het die oppervlaktespannings-effekte van trehalose en of kalsiumbyvoegings tot DPPC-oplossings gemeet deur middel van die ring metode van Du Nouy, In die eerste in vivo studie verbeter oksigenasie en persentasie longaftakking tot dieselfde mate na LPM-l en Exosurf® toediening en word die hipotese van die proefskrif bevestig. In die breë gesien, is die tydsprofiele van LPM-l en Exosurf® ten opsigte van oksigenasie en persentasie longaftakking statisties betekenisvol beter en van 'n sneller aard, as die tydsprofiele van dieselfde indekse na die toediening van fisiologiese soutoplossing of LPM-2. Die tydsprofiel van dinamiese longvervormbaarheid, na die toediening van LPM-I of Exosurf®, is dieselfde, maar betekenisvol beter as die vervormbaarheid na toediening van LPM-2 of fisiologiese soutoplossing. Alhoewel die oksigenasie indekse in die geval van LPM-l en Exosurf® betekenisvol verbeter oor die studietydperk, vind volkome herstel tot die basislynwaardes (voor spoeling) nie plaas nie. Bykomend, geen van die surfaktante het na toediening enige noemenswaardige verbetering in longvervormbaarheid tot gevolg gehad nie. Die rede vir die swakker vertoning van LPM-2 en Exosurf is onbekend en sal in opvolg studie ondersoek word. In die tweede in vivo studie is dit duidelik dat trehalose op sy eie, 'n oneffektiewe surfaktant is aangesien die preperaat na toediening geen verbetering teweegbring ten opsigte van oksigenasie indekse, persentasie longaftakking, of long-dinamiese vervormbaarheid nie. Die toevoeging van trehalose tot LPM-2, om LPM-l te lewer, neem wel die aktiwiteit van LPM-l tot dieselfde in vivo vlak as dié van kommersiële Exosurf®, maar slaag nie daarim om 'n hoër fisiologiese in vivo aktiwiteit as dié produk te bereik nie. Die diere wat met fisiologiese soutoplossing behandel is toon geen verbetering in enige fisiologiese parameter nie. Die in vitro resultate wat verkry is deur die Du Nouy tensiometer toon hoër gemiddelde ordinaat oppervlaktespannings waardes vir 'n formule wat slegs uit DPPC bestaan, asook vir 'n mengsel van DPPC + trehalose. Die helling van die grafieke van hierdie oplossings is ook kleiner as die van die ander formulas wat daarop dui dat DPPC op sigself, en DPPC + trehalose, weinig vermoë het om oppervlaktespanning te verminder. Daarteenoor verlaag die volgende oplossings die oppervlaktespanning ten opsigte van gedistilleerde water betekenisvol en wel in In konsentrasie afhanklike manier by beide 21°C en 3rc: LMP-I-, LPM-2-, DPPC + trehalose + tyloxapol + CaCf2-, en LPM-2 + CaCf2. Die prominentste ligmikroskopiese bevindinge van die longe van die diere sluit in: Algemene limfvat dilatasie, stuwing, en long neutrofiel infiltrasie. Betreffende hierdie histologiese bevindinge is daar geen verskille aangetoon tussen die groepe nie. Hialienmembrane was teenwoordig in al die groepe, maar betekenisvol meer in die groep wat fisiologiese soutoplossing ontvang as vervangingsterapie. In die tweede in vivo studie is daar 'n betekenisvolle styging in die neutrofiel- en daling in makrofaagtelling, van die brongoalveolêre vloeistof spoeling in al drie die groep aangetoon. Terselfdertyd vind geen noemenswaardige daling in die perifêre (sistematiese) neutrofieltelling plaas nie. Hierdie bevindinge dui daarop dat die brongoalveolêre selveranderinge toegeskryf kan word aan verwerwing van neutrofiele vanuit 'n longstoringspoel eerder as rekrutering vanuit die sistemiese sirkulatoriese poel. Surfaktant (LPM-l), behandeling het geen betekenisvolle vermindering in long inflammasie teweeggebring nie. Epiteelskade was 'n algemene ligmikroskopiese bevinding in al die groepe. Die samestelling van die brongoalveolêre vloeistof verander na installering van LPM-I. Die prominentste verandering word waargeneem in die vetsuur samestelling terwyl die DPPC waardes onveranderd bly. Die vetsuur, palmitiensuur (palmitic acid), (CI6:0), verhoog betekenisvol na toediening van LPM-l. Daarteenoor verminder die konsentrasie van C16:1, C18:0 en C18:2. In kontras met vorige studies, beskryf die huidige studie hoër konsentrasies van fosfatidieletanolamien, moontlik as gevolg van tegniese verskille in die metingsmetodes. 'n Betekenisvolle verlaging in die fosfatidielcholine:sfingomiëlien (PC/SM) verhouding word waargeneem tussen die eerste en die finale longspoeling van die trehalose-groep, terwyl dit onveranderd bly in die diere wat LPM-1 of fisiologiese soutoplossing ontvang.

No description available.

Bakgrund: Att arbeta som specialistsjuksköterska inom intensivvård innebär att du kommer möta patienter som vårdas i respirator. En respiratorbehandling är många gånger livräddande, men lång respiratorbehandling associeras även med flera komplikationer och ett stort lidande för den enskilde patienten. Fundamentals of Care (FoC) kan användas som ett stöd för att tillhandahålla en personcentrerad grundläggande omvårdnad. På grund av de komplexa kraven på urträning är det särskilt viktigt att identifiera och tillgodose patienters grundläggande vårdbehov under urträningsprocessen. Syfte: Syftet är att beskriva intensivvårdssjuksköterskors erfarenheter av omvårdnadsåtgärder som underlättar patientens urträning ur respirator utifrån FoC. Metod: En kvalitativ intervjustudie med deduktiv ansats. Totalt rekryterades åtta informanter från två intensivvårdsavdelningar på ett universitetssjukhus i Mellansverige. Insamlad data analyserades med en kvalitativ innehållsanalys enligt Graneheim och Lundman (2004). Resultat: Tre kategorier presenteras i resultatet med utgångspunkt i FoC: etablerad vårdrelation, grundläggande vårdbehov och vårdkontext. Resultatet visade att intensivvårdssjuksköterskorna upplevde att närvaro bidrog till trygghet för patienten, och att kontinuitet i vårdandet kunde underlätta urträningsprocessen. Intensivvårdssjuksköterskorna belyste även vikten av en personcentrerad vård och individanpassad information som viktiga omvårdnadsåtgärder i urträningsprocessen. Slutsats: Genom att tillämpa delarna i FoC kan ramverket fungera som en vägledning för att tillhandahålla en personcentrerad omvårdnad i takt med urträningsprocessen. Att beskriva omvårdnadsåtgärder som kan underlätta urträning ur respirator kan bidra till att göra urträningsprocessen skonsammare för den enskilde patienten. / Background: Working as a critical care nurse means encountering patients undergoing mechanical ventilation. Mechanical ventilation is often life-saving, however prolonged mechanical ventilation is also associated with several complications and patient suffering. Fundamentals of Care (FoC) can be used as a guidance to provide person-centered care. Given the complex demands of weaning, it is important to identify and address patients' basic care needs during the weaning process. Aim: The aim is to describe critical care nurses’ experiences of nursing interventions facilitating the patient's weaning from mechanical ventilation based on FoC. Method: A qualitative interview study with a deductive approach. A total of eight informants were recruited from two critical care units at a university hospital in central Sweden. Collected data were analyzed using qualitative content analysis following Graneheim and Lundman (2004). Result: Three categories are presented in the results based on FoC: relationship, integration of care and context of care. The results showed that critical care nurses experienced that presence contributed to providing a sense of security for the patient, and that continuity in care could facilitate the weaning process. Critical care nurses also highlighted the importance of person-centered care and information as important nursing interventions in the weaning process. Conclusion: By applying the components of FoC, the framework can serve as guidance for providing person-centered care during the weaning process. Describing nursing interventions that can facilitate weaning can contribute to making the weaning process gentler for the patient.

Palliative care is of value to the quality of life in people with terminal conditions when initiated early. The purpose of this literature review was to identify barriers to early initiation of palliative care consultation. The secondary purpose was to examine characteristics that prompt palliative care consultation. The TLC model of palliative care was used to explore palliative care in the critical care setting in people with terminal conditions. The concepts of the model support optimal palliative care as collaborative and comprehensive, with shared decisions made by the patient, practitioners, and loved ones. A literature review was conducted to identify common barriers to early initiation of palliative care consults in the critical care setting for people with terminal conditions. Peer-reviewed articles were retrieved from the EBSCOhost, Medical Literature On-Line (Medline), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Elsevier databases to evaluate their relevance to palliative care in the critical care setting. Twelve preliminary studies were selected for review per the inclusion criteria. Eleven studies identified education and legal factors as barriers. Six studies identified patient and family perceptions as barriers. Five studies identified practitioner-related bias as a significant barrier to consultation. Of the twelve articles reviewed, ten articles referred to palliative care in the adult ICU setting. Two articles included in the review examined barriers to palliative care in the neonatal and pediatric settings. The analysis of the data identified three categories as barriers to initiation of end-of-life care: practitioner-related bias, patient and family perceptions, and education and legal factors after a synthesis of the relevant literature was performed. Analysis of the articles suggests early identification of potential diagnoses for palliative consultation beginning in the intensive care unit (ICU) can improve symptom management, support, patient- centered care, and quality of life for people with terminal conditions. Barriers related to all three categories dominated the literature, with the most prominent being barriers related to education and legal factors. Results indicate that development and implementation of a palliative care referral tool can increase consultation for patients in the critical care setting with terminal conditions. Further education on the topic can increase understanding of palliative care services and improve provision of palliative care through early referrals and consultation.

The aim of the study was to describe the perceptions of critical care nurses concerning family witnessed resuscitation, presenting arguments for or against the practice thereof. A quantitative, descriptive and exploratory approach was used. For the study, a non- probability convenience sample of 100 critical care nurses from five critical care units were used. A combined open-ended and closed-ended questionnaire was used. The majority of critical care nurses in the study disapproved of the idea of family witnessed resuscitation. They believed it to be traumatic for relatives, threatening to the resuscitation process and increasing litigation. Although the dominant feeling was one of disapproval, some critical care nurses felt that family witnessed resuscitation was beneficial to relatives. Recommendations for future practice included incorporation of educational programmes for critical care nurses concerning family witnessed resuscitation and providing training to deal with the stresses of family witnessed resuscitation. / Health Studies / M.A (Health Studies)

The aim of the study was to describe the perceptions of critical care nurses concerning family witnessed resuscitation, presenting arguments for or against the practice thereof. A quantitative, descriptive and exploratory approach was used. For the study, a non- probability convenience sample of 100 critical care nurses from five critical care units were used. A combined open-ended and closed-ended questionnaire was used. The majority of critical care nurses in the study disapproved of the idea of family witnessed resuscitation. They believed it to be traumatic for relatives, threatening to the resuscitation process and increasing litigation. Although the dominant feeling was one of disapproval, some critical care nurses felt that family witnessed resuscitation was beneficial to relatives. Recommendations for future practice included incorporation of educational programmes for critical care nurses concerning family witnessed resuscitation and providing training to deal with the stresses of family witnessed resuscitation. / Health Studies / M.A (Health Studies)

Background: Historically, patients with cancer have been perceived as poor candidates for ICU admission. General ICU admission criteria lists cancer patients as low priority in ICU admission depriving them of the care they rightfully deserve. The purpose of this literary synthesis was to examine ICU admission criteria, risk factors, and outcomes of ICU admission in relation to hematological and solid tumor cancers and discuss ways that practitioners and nurses can educate patients with cancer and their families on appropriateness of ICU care. Methods: A total of 768 articles were found in a literature search including all literature from 2005 to 2016 from all countries using the databases CINAHL Plus, MEDLINE, PsycINFO, and Academic Search Premier. These were further narrowed down based on relevancy by topic or reading abstracts. A total of 13 articles utilizing the inclusion and exclusion criteria of the literature search were included in the final literature synthesis. Results: In addition to general ICU admission criteria several other criteria and scores can be helpful in admitting patients with cancer to the ICU including cancer specific criteria, mortality predictor tools, performance status, and ICU trials. Mortality predictors, in combination with other patient characteristics, demonstrated effectiveness to predict outcomes in patients with cancer. Survival rates in hematological and solid tumor cancers have improved from the past, and lower prognostic scores can predict who will have better outcomes. Conclusion: Cancer specific criteria, mortality predictor tools, performance status, and ICU trials in addition to general ICU criteria should be used for admission of cancer patients into ICU. Practitioners and nurses should become familiar with the newest outcomes in patients with cancer to make collaborative informed decisions about ICU admission.

Thesis (MMed)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Introduction: Of the volatile anaesthetic agents, desflurane causes the greatest degree of potentiation of the neuromuscular blocking drugs (NMB). The purpose of this study was to determine whether desflurane prolongs the effects of 3xED95 doses of rocuronium and cisatracurium to the same degree. The two NMB represent potent and less potent classes respectively. Methods: Informed, written consent was obtained from 63 adult patients scheduled for routine surgery. They were randomly allocated to one of four groups to receive either desflurane-sufentanil (end-tidal partial pressure 4.0 kPa) or propofol-sufentanil anaesthesia and either rocuronium (0.9mg/kg) or cisatracurium (0.15mg/kg). All patients received a target-controlled sufentanil infusion (0.5 ng/ml). Neuromuscular blockade was recorded using accelerometry (TOFGUARD ®, Organon) while patients recovered spontaneously to a Train-of-Four ratio of 0.9 (TOFR0.9). Data were analysed using one- and two-way analysis of variance. The main effects were the types of anaesthetic and NMB on indices of recovery. Results: Compared with propofol-sufentanil anaesthesia, mean times to recovery to T125% and TOFR0.9, were prolonged by desflurane-sufentanil (p<0.01). There were no interactions. Mean prolongation of time to TOFR0.9 was 41 min (SD 36) for cisatracurium and 26.6 min (SD 39) for rocuronium. Discussion: Whereas previous studies did not reveal prolongation of the duration of action of rocuronium by desflurane, we demonstrated a statistically significant prolongation of the spontaneous recovery times of both rocuronium and cisatracurium by desflurane. From the data we could not conclude that there was a difference between the two NMB. A power study revealed that in order to detect a difference between times to recovery to TOF0.9, a sample size of 101 subjects per group would be required. Conclusion: Desflurane prolongs the mean time to spontaneous recovery from neuromuscular blockade after 3xED95 doses of both cisatracurium (a potent NMB) and rocuronium (a less potent NMB). There was wide inter-individual variation in times to spontaneous recovery. Any difference in the mean prolongations between the different types of NMB is unlikely to be of clinical importance. / AFRIKAANSE OPSOMMING: Inleiding Van al die vlugtige narkosemiddels veroorsaak desfluraan die grootste mate van potensiasie van die neuromuskulêre blokkeermiddels. Die doel van hierdie studie was om vas te stel of desfluraan wel die effek van driedubbel die ED95 dosis van rokuronium en cisatrakurium tot dieselfde mate sal verleng. Metodiek Geskrewe ingeligte toestemming is verkry van 63 pasiënte wat voorgedoen het vir roetiene chirurgiese prosedures. Pasiënte is lukraak in een van vier groepe ingedeel om of desfluraansufentaniel (eind-gety parsieële druk 4.0 kPa) of propofol-sufentaniel narkose en of rokuronium (0.9 mg/kg) of cisatrakurium (0.15 mg/kg) te ontvang. Alle pasiënte het 'n teiken-beheerde sufentaniel infusie (0.5 ng/ml). Neuromuskulêre blokkade is waargeneem met behulp van aksellerometrie (TOF-GUARD, Organon) terwyl pasiënte spontaan herstel het tot “reeks-van-vier” verhouding (Engels “Train-of-four” ratio) 0.9 (TOFR0.9). Data analise is gedoen met behulp van een- en tweerigting analise van variansie. Resultate Desfluraan-sufentaniel het die gemiddelde hersteltyd tot T125% en TOFR0.9 verleng in vergelyking met propofol-sufentaniel. Geen interaksies is waargeneem nie. Gemiddelde verlenging van TOFR0.9 vir cisatrakurium was 41 minute (standaardafwyking 36) en vir rokuronium 26.6 minute (standaardafwyking 39). Bespreking Vorige studies kon nie vasstel of desfluraan die werkingsduur van rokuronium verleng nie. Ons het in hierdie studie vasgestel dat desfluraan wel 'n statisties beduidende verlenging in die hersteltyd van beide rokuronium en cisatrakurium veroorsaak. Ons kon egter nie 'n verskil tussen die twee neuromuskulêre agente aandui nie. 'n onderskeidingsvermoëstudie het getoon dat ten minste 101 pasiënte per groep benodig sou word om 'n beduidende verskil tussen die hersteltye tot TOFR0.9 te verkry. Gevolgtrekking Desfluraan verleng die gemiddelde hersteltyd tot spontane herstel van neuromuskulêre blokkade na driedubbele ED95 dosisse van beide cisatrakurium en rokuronium. Daar was egter groot interindividuele variasie ten opsigte van spontane hersteltyd. Enige verskille in die gemiddelde verlenging is onwaarskynlik van kliniese belang.

Dissertation (MD)--Stellenbosch University, 2000. / ENGLISH ABSTRACT: Acute renal failure still is, with the exception of cardiac deaths, the most important pathological process associated with perioperative mortality in patients operated for abdominal aortic aneurysms. The intraoperative change in renal blood flow (RBF) and glomerular function have been investigated in human and animal models, particularly over the past 15 years. Despite large variation in study populations, measurement techniques and study designs in general, a significant body of evidence has developed which suggests infrarenal aortic clamp-induced renal ischemia to be the cause of postoperative acute renal failure when this complication does occur. It is rather surprizing then that, despite some recent studies which have reported on various pharmacological interventions to prevent intraoperative renal ischemia (with variable success), very little has apparently been done to unravel the pathogenesis and exact pathophysiology of this potentially lethal complication. Although a number of investigators suggest the possibility of hormonal involvement (particularly reninangiotensin, antidiuretic hormone (ADH) and catecholamines) in the process, the exact role of these mediators have not been explored (or reported) in a structured fashion. In an initial human study, renal hemodynamics and function were measured from the preoperative period, during the intraoperative phase and at least until 4 hours after aortic unclamping. To investigate the possibility of a temporal relationship between renal changes and fluctuations in hormonal concentrations, plasma concentrations of relevant hormones were determined at every sampling period where renal parameters were measured. The decrease in RBF and glomerular filtration rate (GFR) which we demonstrated to coincide with infrarenal aortic cross clamping, is consistent with results previously published. We demonstrated persistence of the impairment of these parameters as long as 4 hours into the postoperative phase; which has previously only been reported for the period until immediately after aortic unclamping with the abdomen still open. The persistence of a depressed GFR until the time of discharge of patients is cause for concern, particularly in patients with compromised renal function prior to surgery. Of the measured hormones with a potential influence on RBF and nephron function, renin was the only mediator where changes in plasma concentrations coincided with the depression of RBF and GFR after aortic cross clamping. The design of our study did not allow us to conclude whether the concomitant increase in angiotensin II was primarily responsible for the change in renal hemodynamics, or whether the raised renin (and angiotensin) levels were stimulated by the decrease in RBF induced by another mechanism. In another patient group, we demonstrated that the combination of mannitol and dopamine provided no protection against the deleterious effects of aortic cross clamping. In fact, the high urine volumes produced under the influence of these agents (which did not correlate with RBF at the corresponding periods), is likely to prompt a false sense of security. Given the lack of any objective benefit afforded by these agents, their use in these clinical circumstances should be discouraged. The animal studies were aimed at elucidation of the exact role of angiotensin in the pathogenesis and pathophysiology of the renal changes associated with infrarenal aortic clamping, as well as the interaction of angiotensin with other modulators for which an interactive relationship had been described previously under other experimental and/or clinical circumstances. The first study showed that, although renin (and thus angiotensin) concentrations were high after aortic unclamping, the hormone had no pathogenic or pathophysiological role of significance in the observed renal changes during this period (since blocking angiotensin II activation by the prevention of renin release, or by inhibiting the conversion enzyme, did not prevent a substantial decrease in RBF or GFR during that period). Preventing angiotensin II activation did, however, prevent renal changes during aortic clamping. This beneficial effect did not establish a primary role for angiotensin during that period, since the favourable influence could also (at least partially) be explained by prevention of the permissive influence of angiotensin on other vasoconstrictors and/or other vasodilatory influences of ACE inhibition and [1- blockade which are unrelated to angiotensin. This study did indicate that (at least partially) different mechanisms are responsible for the renal changes seen during aortic clamping, and after aortic unclamping. The second study explored the role of calcium in the renal pathophysiological changes during aortic clamping and after unclamping. The protective influence effected by the administration of a Ca2 + -blocker suggest the dependence of the renal vasoconstrictive and glomerular pathophysiological process( es) on the cellular influx of Ca2 + through voltage-gated channels. It unfortunately provides no definitive insight into the primary instigators of these processes. However, it does offer a clinically useful method of preventing these changes and protecting the kidney against ischemic injury during abdominal aortic surgery. The third component of the animal studies demonstrates the importance of the protective effect of renal prostaglandins during the specific experimental (and probably also the clinical) circumstances. Again, it does not provide definitive information on the mediators responsible for the renal changes, since the deleterious effects of numerous endogenous substances have previously been shown to be counterbalanced by intrarenal synthesis of prostaglandins under various experimental and clinical circumstances. The extent of the pathophysiological and ultrastructural changes which occurred under the influence of a NSAID does, however, suggest that these drugs should not be used under these clinical circumstances. The last component of the study provides evidence that angiotensin only plays a secondary/supplementary role in the renal pathophysiological process even during aortic clamping. This may explain the contradictory evidence regarding the potential beneficial effect of ACE inhibition (on renal hemodynamics and glomerular function) during abdominal aortic surgery (Licker et al. 1996, Colson et al. 1992a). Based on our studies, ACE inhibition can not be supported for this purpose. / AFRIKAANSE OPSOMMING: Akute nierversaking is met die uitsondering van kardiale sterftes, steeds die belangrikste patologiese proses wat geassosieer is met perioperatiewe mortaliteit in pasiënte wat opereer word vir abdominale aorta aneurismes. Die intraoperatiewe veranderinge in renale bloedvloei (NBV) en glomerulêre funksie is die afgelope 15 jaar ondersoek en gerapporteer in pasiënte- sowel as diere-modelle. Ten spyte van groot variasies in studie-populasies, meettegnieke en ontwerp van studies in die algemeen, dui 'n wesenlike hoeveelheid getuienis daarop dat infrarenale klemming van die aorta renale isgemie induseer, wat die oorsaak is van postoperatiewe akute nierversaking wanneer hierdie komplikasie voorkom. Dit is verbasend dat, ten spyte van sommige onlangse studies wat rapporteer oor 'n verskeidenheid farmakologiese ingrepe om intraoperatiewe renale isgemie te voorkom (met wisselende sukses), baie min oënskynlik gedoen is om die patogenese en die presiese patofisiologie van hierdie potensieel dodelike komplikasie te ontrafel. Hoewel verskeie outeurs die moontlikheid van hormonale betrokkenheid (veral renienangiotensien, antidiuretiese hormoon en katekolamiene) in hierdie proses suggereer, is die presiese rol van hierdie mediators nog nie op 'n gestruktureerde wyse ondersoek (of rapporteer) nie. In ons aanvanklike pasiënte-studie is renale hemodinamika en -funksie gemeet vanaf die preoperatiewe periode, gedurende die intra-operatiewe fase en tot minstens vier uur na ontklemming van die aorta. Serumkonsentrasies van relevante hormone is bepaal tydens elke metingsperiode waar renale parameters gemeet is, ten einde die moontlikheid van 'n temporale verwantskap tussen renale veranderinge en variasies in hormoonkonsentrasies te ondersoek. Die vermindering in NBV en glomerulêre filtrasiespoed (GFS) wat ons aangetoon het om saam te val met infrarenale aortaklemming, stem ooreen met resultate wat tevore deur ander navorsers publiseer is. Ons het aangetoon dat die inkorting van hierdie parameters voortduur tot minstens vier uur na aorta-ontklemming. Hierdie veranderinge is tevore slegs rapporteer vir periodes tot kort na aorta-ontklemming voor sluiting van die buikwond. Die feit dat die GFS steeds verlaag is met ontslag van hierdie pasiënte, skep rede tot kommer, veral in pasiënte wat alreeds ingekorte nierfunksie het voor die chirurgiese prosedure. Van die gemete hormone wat moontlik 'n invloed sou kon uitoefen op NBV eh nefronfunksie, was renien die enigste waarvan verandering in plasmakonsentrasies saamgeval het met die onderdrukking van NBV en GFS na aortaklemming. Die ontwerp van ons studie het ons nie toegelaat om 'n besliste uitspraak te maak of die geassosieerde verhoging in angiotensien II primêr verantwoordelik was vir die verandering in renale hemodinamika, of dat die verhoogde renien (en angiotensien) bloedvlakke moontlik sekondêr stimuleer is deur die verandering in NBV wat deur 'n ander meganisme induseer is. In 'n ander pasiëntegroep het ons aangetoon dat die kombinasie van mannitol en dopamien geen beskerming verleen het teen die nadelige effekte van aorta-klemming nie. Die groot volumes uriene wat uitgeskei is onder die invloed van hierdie middels (wat nie korreleer het met NBV tydens ooreenstemmende periodes nie), het inderwaarheid 'n ontoepaslike gerustheid uitgelok. Weens die ooglopende gebrek aan objektiewe voordeel wat verleen word deur hierdie middels, behoort hulle gebruik tydens hierdie kliniese omstandighede ontmoedig te word. Die doel van die diere studies was die identifisering van die presiese rol van angiotensien in die patogenese en patofisiologie van die renale veranderinge geassosieer met infrarenale aortaklemming, sowel as die interaksie van angiotensien met ander modulators waarvoor 'n interaktiewe verwantskap voorheen beskryf is onder eksperimentele en/of kliniese omstandighede. Die eerste studie het getoon dat alhoewel renien (en dus angiotensien) konsentrasies hoog was na aorta-ontklemming, die hormone geen betekenisvolle patogenetiese of patofisiologiese rol in die waargenome renale veranderinge gedurende hierdie periode het nie (aangesien blokkade van angiotensien aktivering deur voorkoming van renien vrystelling, of deur inhibisie van angiotensien omsettingsensiem (AOE), nie 'n daling in NBV of GFS kon voorkom nie). Voorkoming van angiotensien II aktivering het egter wel renale verandering voorkom gedurende aortaklemming. Dié voordelige effek het nie 'n primêre rol vir angiotensien gedurende die periode bevestig nie, aangesien die gunstige invloed ook (ten minste gedeeltelik) verduidelik kon word deur die voorkoming van die fassiliterende invloed van angiotensien op ander vasokonstriktore en/of ander vasodilator-invloede van die onderdrukking van AOE en ïs-blokkers (wat geen verband het met angiotensien of die blokkade daarvan nie). Die studie het aangetoon dat (ten minste gedeeltelik) verskillende meganismes verantwoordelik is vir renale veranderinge wat gesien is gedurende aortaklemming en na -ontklemming. Die tweede studie het die rol van kalsium in die renale patofisiologiese veranderinge gedurende aortaklemming en na ontklemming ondersoek. Die beskermende invloed wat deur die toediening van Ca2 + -blokkers bewerkstellig is, het bevestig dat die renale vasokonstriktoriese en glomerulêre patofisiologiese prosesse afhanklik is van sellulêre influks van kalsium deur spannings-afhanklike kannale. Dit het ongelukkig geen definitiewe insig verleen ten opsigte van die primêre inisieerders van die proses nie. Dit verskaf nogtans 'n bruikbare kliniese metode om daardie veranderinge te voorkom en die niere teen isgemiese besering gedurende abdominale aorta-chirurgie te beskerm. Die derde komponent van die diere-studies demonstreer die belangrikheid van die beskermende effek van renale prostaglandiene tydens die spesifieke eksperimentele (en waarskynlik ook die kliniese) omstandighede. Weereens gee dit nie definitiewe inligting oor die bemiddelaars wat verantwoordelik is vir die renale veranderinge nie, aangesien die skadelike effekte van verskeie endogene stowwe voorheen aangetoon is om beperk of voorkom te word deur die intrarenale vrystelling van prostaglandiene. Die omvang van die patofisiologiese en ultrastrukturele veranderinge wat ontstaan het onder die invloed van nie-steroïed anti-inflammatoriese middels (wat gebruik is om prostaglandien sintese te inhibeer), dui aan dat hierdie middels vermy moet word onder soortelyke kliniese omstandighede. Die laaste komponent van die studie verskaf 'n sterk aanduiding dat angiotensien slegs 'n sekondêre/aanvullende rol speel in die renale patofisiologiese proses, selfs gedurende aortaklemming. Dit mag die weersprekende getuienis oor die potensiële voordeel van AOE onderdrukking (op renale hemodinamika en glomerulêre funksie) gedurende abdominale aortachirurgie (Licker et al. 1996, Colson et al. 1992a) verklaar. Gebaseer op ons studies, kan AOE onderdrukking nie ondersteun word vir hierdie doel nie.

Accurate mortality prediction in intensive care units (ICUs) allows for the risk adjustment of study populations, aids in patient care and provides a method for benchmarking overall hospital and ICU performance. ICU risk-adjustment models are primarily comprised of an integer severity of illness score which increases with increasing patient risk of mortality. First published in the 1980s, the improvements to these scores primarily consisted of increasing the dimensionality of the model, and hence also increasing their complexity. This thesis aims to improve upon these models. First, the field is surveyed and the major models for risk-adjusting critically ill patient cohorts are identified including the acute physiology score (APS) and the simplified acute physiology score (SAPS). A key component of model performance is data preprocessing. The effect of preprocessing ICU data is quantified on a dataset of 8,000 ICU patients, and it is shown that after preprocessing to remove extreme values a logistic regression (LR) model performed competitively (AUROC of 0.8633) with the more complex machine learning model; a support vector machine (SVM) which had an AUROC of 0.8653. For validation, model development was repeated in a larger database containing over 80,000 patients admitted to 89 ICUs in the United States. Results were similar (AUROC of 0.8895 for the LR vs 0.8917 for the SVM) but showed the performance gain when using automated outlier rejection is less pronounced in well quality controlled datasets (0.8883 for LR without rejection). It is hypothesised from this that simpler models can perform competitively with more complicated models, while having a greatly reduced burden of data collection. A severity score is developed on the large multi-center database using a Genetic Algorithm and Particle Swarm Optimisation. The severity score, named the Oxford Acute Severity of Illness Score (OASIS), is shown to outperform the APS III (AUROC 0.837 vs 0.822) and perform competitively with APACHE IV when used as a covariate in a regression model (AUROC 0.868 vs 0.881). The severity score requires only 10 variables (58&percnt; as many as APS III), reducing the burden of quality control and data collection. These variables are routinely collected in critical care by continuous monitors and do not include comorbidities, diagnosis or laboratory measurements. The severity score is then externally evaluated in an American hospital and shown to discriminate well (AUROC 0.790 vs. 0.782 for the APS III) with excellent calibration. Finally, the severity score was evaluated in an English hospital and compared to other severity scores. OASIS again had excellent calibration and discrimination (AUROC 0.776 vs 0.750 for APS III) whilst requiring a much smaller number of variables. OASIS has many applications, including both simplifying data collection for studies and improving the risk assessment therein.