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Biomedical subjects

R M Grounds

Publications and source records attributed to R M Grounds.

At least 19 recordsLinked to original sources

Performing perioperative optimization of the high-risk surgical patient.

Perioperative risk of death after general surgery is quoted as overall less than 1%. However, each individual's risk varies widely according to many identified factors with some having a significantly increased risk of a worse outcome. The observation that manipulating and targeting certain physiological parameters in selected patients can influence this risk has been reported in numerous studies. Yet it is still not widely practised to assist the process, despite the availability of various invasive and non-invasive monitors. This may be in part because of a lack of experience with the practicalities of perioperative optimization, and lack of knowledge in applying currently available tools. This article aims to try and address this deficit and increase awareness of how and when to utilize monitoring equipment to achieve optimal results for the patients we treat.

Algorithms↗

Use of activated recombinant coagulation factor VII in patients undergoing reconstruction surgery for traumatic fracture of pelvis or pelvis and acetabulum: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Activated recombinant coagulation factor VII (rFVIIa) effectively prevents and controls bleeding in patients with coagulopathy. Data show that rFVIIa may reduce blood loss and eliminate the need for transfusion in patients with normal haemostasis undergoing major surgery. We assessed the efficacy of rFVIIa in patients with normal haemostasis undergoing repair surgery of major traumatic fracture of the pelvis or the pelvis and acetabulum, who were expected to have a large volume of blood loss. METHODS: We performed a double-blind, randomized, placebo-controlled trial involving 48 patients undergoing major pelvic-acetabular surgery. Patients were randomized to receive an i.v. bolus injection of rFVIIa 90 microg kg(-1) or placebo as add-on therapy at the time of the first skin incision. All patients also received intraoperative salvaged red blood cells (RBC). RESULTS: There was no significant difference in the total volume of perioperative blood loss, the primary outcome variable, between the rFVIIa and placebo groups. In addition, there were no differences between the two groups in the total volume of blood components, including salvaged RBC transfused, number of patients requiring allogeneic blood components, total volume of fluids infused, total operating time, time taken after entry to the intensive care unit to reach normal body temperature and acid-base status, and time spent in hospital. No adverse events, in particular thromboembolic events, were reported in either group. CONCLUSIONS: In patients with normal haemostasis undergoing repair surgery of traumatic pelvic-acetabular fracture, the prophylactic use of rFVIIa does not decrease the volume of perioperative blood loss.

Acetabulum↗

The hormonal and inflammatory responses to pelvic reconstructive surgery following major trauma.

Patients undergoing trauma sustain an initial injury followed by further physiological challenges during surgery. Plasma osteocalcin (OC), a marker of osteoblastic activity, declines after major surgery. Increased cortisol secretion, and other components of the perioperative stress response, may play a role in mediating this response. We have examined the osteocalcin, hormonal and cytokine responses in twenty patients undergoing post-traumatic pelvic reconstruction surgery. We measured plasma osteocalcin, serum cortisol, bone specific alkaline phosphatase (BSAP), IL-6, IL-8, IL-10, plasma epinephrine and norepinephrine concentrations for up to 3 days after surgery. We recorded an increase in IL-6, IL-10 and epinephrine concentrations perioperatively and a fall in OC and BSAP concentrations. There were no significant changes in cortisol or IL-8 concentrations. Patients undergoing pelvic reconstruction surgery following trauma have a preserved inflammatory and catecholamine response but the cortisol response may be obtunded. Osteocalcin concentrations are affected by factors other than glucocorticoids.

Adolescent↗

Calibration of three capnographs for use with helium and oxygen gas mixtures.

Capnography is considered essential in the management of mechanically-ventilated patients. Helium, as an adjunct to mechanical ventilation, is the subject of renewed interest and used increasingly. However, helium affects the performance of infrared capnometry. We constructed a simple device to generate variable mixtures of helium, oxygen and carbon dioxide within the normal physiological range, and tested the performance of two side-stream and one in-line capnographs. We found that addition of helium to the gas mixture caused all three capnographs to underestimate the concentration of carbon dioxide. The underestimation increased as the proportion of helium increased. The maximum underestimation (30%) occurred in a 79:21 helium/oxygen mixture.

Calibration↗

The strong ion gap does not have prognostic value in critically ill patients in a mixed medical/surgical adult ICU.

OBJECTIVE: To examine whether the strong ion gap (SIG) or standard base excess corrected for abnormalities of serum chloride and albumin (BE(UA)) can predict outcome and to compare the prognostic abilities of these variables with standard base excess (SBE), anion gap (AG), pH, and lactate, the more traditional markers of acid-base disturbance. DESIGN: Prospective, observational study. SETTING: University teaching hospital, general adult ICU. PATIENTS: One hundred consecutive patients on admission to the ICU. MEASUREMENTS AND RESULTS: The anion gap (AG) was calculated and corrected for abnormal serum albumin (AG(corrected)). Serum lactate was measured and SBE, BE(UA), SIG, and APACHE II scores calculated for each patient. 28-day survival was recorded. There was a significant difference between the mean APACHE II (P < 0.001), SBE (P < 0.001), lactate (P = 0.008), AG (P = 0.007), pH (P < 0.001), and BE(UA) (P = 0.009) of survivors and non-survivors. There was no significant difference between the mean SIG (P = 0.088), SIDeff (P = 0.025), and SID app (P = 0.254) between survivors and non-survivors. The pH and SBE demonstrated the best ability of the acid-base variables to predict outcome (AUROC curves 0.72 and 0.71, respectively). Neither of these were as good as the APACHE II score (AUROC 0.76) CONCLUSION: Traditional indices of SBE, BE(UA,) lactate, pH, AG, and APACHE II all discriminated well between survivors and non-survivors. In this group of patients the SIG, SIDeff, and SIGapp appear to offer no advantage in prediction of outcome and their use as prognostic markers can therefore not be advocated.

APACHE↗

Acid-base physiology: the 'traditional' and the 'modern' approaches.

The interpretation and understanding of acid-base dysfunction has recently been revisited. The 'traditional' approach developed from the pioneering work of Henderson and Hasselbalch and is still the most widely used in clinical practice. There are a number of problems identified with this approach, however. The 'modern' approach derives from Stewart's work in physical chemistry. In this review we describe the origins of the traditional approach and discusses related concepts. We then describe Stewart's approach, including how it is derived and how it may be used to classify acid-base derangements. The applications of Stewart's approach to clinical scenarios in intensive care is then discussed briefly before we examine some published clinical studies based on his work.

Acid-Base Equilibrium↗

Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive caret.

BACKGROUND: The pharmacokinetics of the alpha-2 adrenoceptor agonist dexmedetomidine were studied in 10 patients requiring postoperative sedation and mechanical ventilation in the intensive care unit (ICU), and compared with previous volunteer data. METHODS: On arrival in the ICU, sedation with dexmedetomidine was commenced with a loading dose of 2.5 microg kg(-1) h(-1) over 10 min followed by a maintenance infusion of 0.7 microg kg(-1) h(-1) into a central vein. Blood samples for measurement of plasma dexmedetomidine concentrations were taken during and after sedative infusions at predetermined intervals. Pharmacokinetic variables were estimated using non-compartmental methods. In addition, non-linear mixed effects modelling was used to obtain variable estimates not readily attainable from non-compartmental methods. Respiratory and haemodynamic data were recorded to enable correlation of any adverse events with the calculated pharmacokinetic profile. RESULTS: The harmonic mean distribution half-life of dexmedetomidine was 8.6 min and the harmonic mean terminal half-life was 3.14 h. Steady-state volume of distribution averaged 173 litres, clearance averaged 48.3 litres h(-1), and the mean residence time averaged 3.86 h. CONCLUSIONS: Mean dexmedetomidine pharmacokinetic variables seen in postoperative, intensive care patients were similar to those previously found in volunteers, with the exception of the steady-state volume of distribution. A small loading dose provided effective sedation with no adverse events.

Adrenergic alpha-Agonists↗

Base excess and lactate as prognostic indicators for patients admitted to intensive care.

OBJECTIVE: To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. DESIGN: Observational study. SETTING: University teaching hospital general adult intensive care unit. PATIENTS: 148 consecutive patients admitted to the intensive care unit. INTERVENTIONS: Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. MEASUREMENTS AND RESULTS: Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than -4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5%, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. CONCLUSIONS: Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit.

Acid-Base Equilibrium↗

Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit.

We have compared the effects of dexmedetomidine and propofol on endocrine, metabolic, inflammatory and cardiovascular responses in patients in the intensive care unit (ICU) after major surgery. Twenty patients who were expected to require 8 h of post-operative sedation and ventilation were allocated randomly to receive either an infusion of dexmedetomidine 0.2-2.5 microg kg(-1) h(-1) or propofol 1-3 mg kg(-1) h(-1). Arterial pressure, heart rate and sequential concentrations of circulating cortisol, adrenocorticotrophic hormone (ACTH), growth hormone, prolactin, insulin, glucose and interleukin 6 were measured. An ACTH stimulation test was performed in all patients who received dexmedetomidine. Heart rate was significantly lower in the dexmedetomidine patients. There were no differences in arterial pressure, cortisol, ACTH, prolactin and glucose concentrations between the two groups. A positive response to the ACTH stimulation test varied depending on the diagnostic criteria used. The insulin concentration was significantly lower in the dexmedetomidine group at 2 h (P=0.021), although this did not affect blood glucose concentrations. Growth hormone concentrations were significantly higher in dexmedetomidine-treated patients overall (P=0.036), but circulating concentrations remained in the physiological range. Interleukin 6 decreased in the dexmedetomidine group. We conclude that dexmedetomidine infusion does not inhibit adrenal steroidogenesis when used for short-term sedation after surgery.

Adrenal Cortex↗

Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions.

The alpha2 agonist dexmedetomidine is a new sedative and analgesic agent which is licensed in the USA for post-operative intensive care sedation. We compared dexmedetomidine with propofol in patients requiring sedation in intensive care. Twenty adult patients expected to require a minimum of 8 h artificial ventilation after surgery were randomized to receive sedation with either dexmedetomidine or propofol infusions. Additional analgesia, if required, was provided by an alfentanil infusion. Depth of sedation was monitored using both the Ramsay sedation score (RSS) and the bispectral index (BIS). Cardiovascular, respiratory, biochemical and haematological data were obtained. Patients' perceptions of their intensive care stay were assessed using the Hewitt questionnaire. Sedation was equivalent in the two groups [median (interquartile range): RSS, propofol group 5 (4-5), dexmedetomidine group 5 (4-6) (P=0.68); BIS, propofol group 53 (41-64), dexmedetomidine group 46 (36-58); P=0.32], but the propofol group received three times more alfentanil compared with patients sedated with dexmedetomidine [2.5 (2.2-2.9) mg h(-1) versus 0.8 (0.65-1.2) mg h(-1) (P=0.004)]. No differences were found in arterial pressures between the groups, but heart rate was significantly lower in the dexmedetomidine group [mean (SD) 75 (6) vs 90 (4) beats min(-1)]. Extubation times were similar and rapid with the use of both sedative agents [median (range) 28 (20-50) and 29 (15-50) min (P=0.63) respectively for the propofol and dexmedetomidine groups]. No adverse events related to the sedative infusions occurred in either group. Despite ventilation and intubation, patients sedated with dexmedetomidine could be easily roused to cooperate with procedures (e.g. physiotherapy, radiology) without showing irritation. From the clinician's and patient's perspectives, dexmedetomidine is a safe and acceptable sedative agent for those requiring intensive care. The rate pressure product is reduced in patients receiving dexmedetomidine, which may protect against myocardial ischaemia. Dexmedetomidine reduces the requirement for opioid analgesia.

Adrenergic alpha-Agonists↗

Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care.

STATEMENT OF FINDINGS: The respiratory effects of dexmedetomidine were retrospectively examined in 33 postsurgical patients involved in a randomised, placebo-controlled trial after extubation in the intensive care unit (ICU). Morphine requirements were reduced by over 50% in patients receiving dexmedetomidine. There were no differences in respiratory rates, oxygen saturations, arterial pH and arterial partial carbon dioxide tension (PaCO2) between the groups. Interestingly the arterial partial oxygen tension (PaO2) : fractional inspired oxygen (FIO2) ratios were statistically significantly higher in the dexmedetomidine group. Dexmedetomidine provides important postsurgical analgesia and appears to have no clinically important adverse effects on respiration in the surgical patient who requires intensive care.

Adrenergic alpha-Agonists↗

Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit.

Dexmedetomidine, a highly selective and potent alpha2-adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation.

Adolescent↗

A prospective study of the use of a dobutamine stress test to identify outcome in patients with sepsis, severe sepsis, or septic shock.

OBJECTIVE: To more clearly define the relationship between an oxygen flux test, oxygen supply dependency, and outcome in patients with sepsis, severe sepsis, or septic shock. DESIGN: Prospective, interventional clinical trial. SETTING: A teaching hospital general intensive care unit in London, UK. PATIENTS: A total of 36 patients with sepsis, severe sepsis, or septic shock were studied during a 10-month period. INTERVENTIONS: After resuscitation, patients were given an intravenous infusion of dobutamine at 10 microg/kg/min for 1 hr. Cardiac and respiratory variables were measured before the infusion and then while the infusion was in progress. Any patient who was able to increase his or her oxygen consumption by >15% was designated a responder to the test. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, oxygen transport, and lactate measurements were made at baseline and after 1 hr of the dobutamine infusion. All patients were then followed up until hospital discharge. Responders to this test had a hospital mortality of 14%, whereas nonresponders had a mortality of 91% (p<.01). The responders were characterized by being younger (p<.05), having higher Acute Physiology and Chronic Health Evaluation III scores (p<.05), and having a greater requirement for inotropic support (p<.05). After the test, the responders had significantly higher oxygen delivery (p<.01) and oxygen consumption (p<.05) than the nonresponders, as well as a significantly greater temperature increase as a result of the infusion (p<.05). The nonresponders were unable to increase either oxygen delivery or oxygen consumption to the dobutamine. This test was highly predictive of outcome (p<.0001). The identification of an increase in both oxygen delivery and oxygen consumption (oxygen supply dependency) was not associated with a poor outcome. CONCLUSION: A dobutamine oxygen flux test provides evidence of the intrinsic function of cells. The inability of these cells to increase oxidative metabolism during sepsis, as indicated by the dobutamine test, is associated with a high mortality.

Adult↗