Peter Vernon van Heerden

Decrease in proven ventriculitis by reducing the frequency of cerebrospinal fluid sampling from extraventricular drains

OBJECT Ventriculitis associated with extraventricular drains (EVD) increases rates of morbidity and mortality as well as costs. Surveillance samples of CSF are taken routinely from EVD, but there is no consensus on the optimum frequency of sampling. The goal of this study was to assess whether the incidence of ventriculitis changed when CSF sampling frequency was reduced once every 3 days. METHODS After receiving institutional ethics committee approval for their project, the authors compared a prospective sample of EVD-treated patients (admitted 2008-2009) and a historical comparison group (admitted 2005-2007) at two tertiary hospital ICUs. A broad definition of ventriculitis included suspected ventriculitis (that is, treated with antibiotics for ventriculitis) and proven ventriculitis (positive CSF culture). Adult ICU patients with no preexisting neurological infection were enrolled in the study. After staff was provided with an education package, sampling of CSF was changed from daily to once every 3 days. All other management of the EVD remained unchanged. More frequent sampling was permitted if clinically indicated during the third daily sampling phase. RESULTS Two hundred seven patients were recruited during the daily sampling phase and 176 patients when sampling was reduced to once every 3 days. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was lower for the daily sampling group than for the every-3rd-day group (18.6 vs 20.3, respectively; p < 0.01), but there was no difference in mean age (47 and 45 years, respectively; p = 0.14), male or female sex (61% and 59%, respectively; p = 0.68), or median EVD duration in the ICU (4.9 and 5.8 days, respectively; p = 0.14). Most patients were admitted with subarachnoid hemorrhage (42% in the daily group and 33% in the every-3rd-day group) or traumatic head injuries (29% and 36%, respectively). The incidence of ventriculitis decreased from 17% to 11% overall and for proven ventriculitis from 10% to 3% once sampling frequency was reduced. Sampling of CSF once every 3 days was independently associated with ventriculitis (OR 0.44, 95% CI 0.22-0.88, p = 0.02). CONCLUSIONS Reducing the frequency of CSF sampling to once every 3 days was associated with a significant decrease in the incidence of ventriculitis. The authors suggest that CSF sampling should therefore be performed once every 3 days in the absence of clinical indicators of ventriculitis. Reducing frequency of CSF sampling from EVDs decreased proven ventriculitis.

Inhaled diazeniumdiolates (NONOates) as selective pulmonary vasodilators

Selective pulmonary vasodilators cause vasodilatation limited to the pulmonary vasculature, within well-ventilated lung regions. Selective pulmonary vasodilators ideally cause only a minimal effect on the systemic circulation and improve ventilation/perfusion matching. NONOates are a novel group of chemical compounds that spontaneously and continuously release nitric oxide under physiological conditions, over periods of up to 24 h. Inhaled NONOates retain the benefits of gaseous nitric oxide without many of its therapeutic disadvantages. This review focuses on the therapeutic potential of inhaled NONOates in pulmonary hypertension, other lung conditions associated with right ventricular dysfunction and in asthma. The potential toxicity of NONOates is also discussed.

Matching positive end-expiratory pressure to intra-abdominal pressure improves oxygenation in a porcine sick lung model of intra-abdominal hypertension

IntroductionIntra-abdominal hypertension (IAH) causes atelectasis, reduces lung volumes and increases respiratory system elastance. Positive end-expiratory pressure (PEEP) in the setting of IAH and healthy lungs improves lung volumes but not oxygenation. However, critically ill patients with IAH often suffer from acute lung injury (ALI). This study, therefore, examined the respiratory and cardiac effects of positive end-expiratory pressure in an animal model of IAH, with sick lungs.MethodsNine pigs were anesthetized and ventilated (48 +/- 6 kg). Lung injury was induced with oleic acid. Three levels of intra-abdominal pressure (baseline, 18, and 22 mmHg) were randomly generated. At each level of intra-abdominal pressure, three levels of PEEP were randomly applied: baseline (5 cmH2O), moderate (0.5 × intra-abdominal pressure), and high (1.0 × intra-abdominal pressure). We measured end-expiratory lung volumes, arterial oxygen levels, respiratory mechanics, and cardiac output 10 minutes after each new IAP and PEEP setting.ResultsAt baseline PEEP, IAH (22 mmHg) decreased oxygen levels (-55%, P <0.001) and end-expiratory lung volumes (-45%, P = 0.007). At IAP of 22 mmHg, moderate and high PEEP increased oxygen levels (+60%, P = 0.04 and +162%, P <0.001) and end-expiratory lung volume (+44%, P = 0.02 and +279%, P <0.001) and high PEEP reduced cardiac output (-30%, P = 0.04). Shunt and dead-space fraction inversely correlated with oxygen levels and end-expiratory lung volumes. In the presence of IAH, lung, chest wall and respiratory system elastance increased. Subsequently, PEEP decreased respiratory system elastance by decreasing chest wall elastance.ConclusionsIn a porcine sick lung model of IAH, PEEP matched to intra-abdominal pressure led to increased lung volumes and oxygenation and decreased chest wall elastance shunt and dead-space fraction. High PEEP decreased cardiac output. The study shows that lung injury influences the effects of IAH and PEEP on oxygenation and respiratory mechanics. Our findings support the application of PEEP in the setting of acute lung injury and IAH.

Matching positive end-expiratory pressure to intra-abdominal pressure prevents end-expiratory lung volume decline in a pig model of intra-abdominal hypertension

Objective:Intra-abdominal hypertension is common in critically ill patients and is associated with increased morbidity and mortality. In a previous experimental study, positive end-expiratory pressures of up to 15 cm H2O did not prevent end-expiratory lung volume decline caused by intra-abdominal hypertension. Therefore, we examined the effect of matching positive end-expiratory pressure to the intra-abdominal pressure on cardio-respiratory parameters. Design:Experimental pig model of intra-abdominal hypertension. Setting:Large animal facility, University of Western Australia. Subjects:Nine anesthetized, nonparalyzed, and ventilated pigs (48 ± 7 kg). Interventions:Four levels of intra-abdominal pressure (baseline, 12, 18, and 22 mm Hg) were generated in a randomized order by inflating an intra-abdominal balloon. At each level of intra-abdominal pressure, three levels of positive end-expiratory pressure were randomly applied with varying degrees of matching the corresponding intra-abdominal pressure: baseline positive end-expiratory pressure (= 5 cm H2O), moderate positive end-expiratory pressure (= half intra-abdominal pressure in cm H2O + 5 cm H2O), and high positive end-expiratory pressure (= intra-abdominal pressure in cm H2O). Measurements:We measured end-expiratory lung volume, arterial oxygen levels, respiratory mechanics, and cardiac output 5 mins after each new intra-abdominal pressure and positive end-expiratory pressure setting. Main Results:Intra-abdominal hypertension decreased end-expiratory lung volume and PaO2 (−49% [p < .001] and −8% [p < .05], respectively, at 22 mm Hg intra-abdominal pressure compared with baseline intra-abdominal pressure) but did not change cardiac output (p = .5). At each level of intra-abdominal pressure, moderate positive end-expiratory pressure increased end-expiratory lung volume (+119% [p < .001] at 22 mm Hg intra-abdominal pressure compared with 5 cm H2O positive end-expiratory pressure) while minimally decreasing cardiac output (−8%, p < .05). High positive end-expiratory pressure further increased end-expiratory lung volume (+233% [p < .001] at 22 mm Hg intra-abdominal pressure compared with 5 cm H2O positive end-expiratory pressure) but led to a greater decrease in cardiac output (−26%, p < .05). Neither moderate nor high positive end-expiratory pressure improved PaO2 (p = .7).Intra-abdominal hypertension decreased end-expiratory transpulmonary pressure but did not alter end-inspiratory transpulmonary pressure. Intra-abdominal hypertension decreased total respiratory compliance through a decrease in chest wall compliance. Positive end-expiratory pressure decreased the respiratory compliance by reducing lung compliance. Conclusions:In a pig model of intra-abdominal hypertension, positive end-expiratory pressure matched to intra-abdominal pressure led to a preservation of end-expiratory lung volume, but did not improve arterial oxygen tension and caused a reduction in cardiac output. Therefore, we do not recommend routine application of positive end-expiratory pressure matched to intra-abdominal pressure to prevent intra-abdominal pressure–induced end-expiratory lung volume decline in healthy lungs.

Commonly applied positive end-expiratory pressures do not prevent functional residual capacity decline in the setting of intra-abdominal hypertension: a pig model

IntroductionIntra-abdominal hypertension is common in critically ill patients and is associated with increased morbidity and mortality. The optimal ventilation strategy remains unclear in these patients. We examined the effect of positive end-expiratory pressures (PEEP) on functional residual capacity (FRC) and oxygen delivery in a pig model of intra-abdominal hypertension.MethodsThirteen adult pigs received standardised anaesthesia and ventilation. We randomised three levels of intra-abdominal pressure (3 mmHg (baseline), 18 mmHg, and 26 mmHg) and four commonly applied levels of PEEP (5, 8, 12 and 15 cmH2O). Intra-abdominal pressures were generated by inflating an intra-abdominal balloon. We measured intra-abdominal (bladder) pressure, functional residual capacity, cardiac output, haemoglobin and oxygen saturation, and calculated oxygen delivery.ResultsRaised intra-abdominal pressure decreased FRC but did not change cardiac output. PEEP increased FRC at baseline intra-abdominal pressure. The decline in FRC with raised intra-abdominal pressure was partly reversed by PEEP at 18 mmHg intra-abdominal pressure and not at all at 26 mmHg intra-abdominal pressure. PEEP significantly decreased cardiac output and oxygen delivery at baseline and at 26 mmHg intra-abdominal pressure but not at 18 mmHg intra-abdominal pressure.ConclusionsIn a pig model of intra-abdominal hypertension, PEEP up to 15 cmH2O did not prevent the FRC decline caused by intra-abdominal hypertension and was associated with reduced oxygen delivery as a consequence of reduced cardiac output. This implies that PEEP levels inferior to the corresponding intra-abdominal pressures cannot be recommended to prevent FRC decline in the setting of intra-abdominal hypertension.

The role of femoral venous pressure and femoral venous oxygen saturation in the setting of intra-abdominal hypertension: a pig model

Femoral venous access is frequently used in critically ill patients. Because raised intra-abdominal pressure (IAP) is also frequently found in this group of patients, we examined the impact of IAP and positive end-expiratory pressure (PEEP) on femoral venous pressure (FVP) and femoral venous oxygen saturation (Sfvo2) in an animal model. Thirteen adult pigs received standardized anesthesia and ventilation. Randomized levels of IAP (3 [baseline], 18, and 26 mmHg) were applied, with levels of PEEP (5, 8, 12, and 15 cmH2O) applied randomly at each IAP level. We measured bladder pressure (IAP), superior vena cava pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, FVP, mixed venous oxygen saturation (Svo2), and Sfvo2. We found that FVP correlated well with IAP (FVP = 4.1 + [0.12 × PEEP] + [1.00 × IAP]; R2 = 0.89, P < 0.001) with a moderate bias and precision of 5.0 and 3.8 mmHg, respectively. Because the level of agreement did not meet the recommendations of the World Society of Abdominal Compartment Syndrome, FVP cannot currently be recommended to measure IAP, and further clinical trials are warranted. However, a raised FVP should prompt the measurement of the bladder pressure. Femoral venous oxygen saturation did correlate neither with Svo2 nor with abdominal perfusion pressure. Therefore, Sfvo2 is of no clinical use in the setting of raised IAP.

The safety of aerosolized diethylenetriamine nitric oxide adduct after single-dose administration to anesthetized piglets and multiple-dose administration to conscious rats

Diethylenetriamine nitric oxide adduct (DETA/NO) is a slow-release NO donor. It has been shown to be a selective pulmonary vasodilator in acute pulmonary hypertension. However, its potential toxicity after inhalation is unknown. This study investigated the potential toxicity of aerosolized DETA/NO after single- and multiple-dose exposure in animals. In the first part of the study, a single dose of DETA/NO (60 micromol) or placebo was aerosolized into the lungs of anesthetized piglets. Arterial methemoglobin and serum nitrite (NO2-) concentrations were measured after exposure. In the second part of the study, rats were exposed to aerosolized DETA/NO (60 micromol) or placebo for 7 days, and animals were euthanized 1, 3, 7, and 14 days after the first exposure. Serum NO2- and plasma surfactant protein B (SP-B) concentrations were measured. In both studies, acute lung inflammation was evaluated histopathologically (polymorphonuclear leucocytes (PMN) infiltration) and by measuring lung wet to dry weight ratio (LWDR). The tracheas of rats, which had the highest exposure, were further examined for ultrastructural changes using electron microscopy. In both rats and pigs, serum NO2- concentrations were elevated in all the DETA/NO-treated animals, indicating significant exposure to DETA/NO. Arterial methemoglobin was not increased by DETA/NO treatment. In the rats, plasma SP-B was not elevated by DETA/NO treatment. In addition, DETA/NO had no effects on PMN infiltration or LWDR in either animal model nor on the ultrastructure of large airways in rats. This study shows no evidence of pulmonary or hematological toxicity following single or repeated doses of DETA/NO in animals.

The ratio of polymorphonuclear leucocytes (PMN) to non-PMN cells: a novel method of assessing acute lung inflammation

Polymorphonuclear leucocyte (PMN) numbers are an indicator of the degree of acute lung inflammation. However, there is no standardized system for accurately quantifying their numbers in tissue sections. Also, the effect of lung inflation on the quantification of PMNs is usually overlooked. Lung specimens obtained from clinical biopsies are usually deflated, while inflated lung tissue is commonly used in experimental studies. We report a method, which is independent of the degree of inflation, for measuring the degree of PMN infiltration in the both inflated and non-inflated lungs. Using light microscopy, we counted the numbers of PMN and non-PMN cells in 240 fields from each of five inflated and five non-inflated lung sections and calculated a ratio of PMN: non-PMN cells (the PMN ratio). The effect on accuracy and precision of number of fields counted was investigated by randomly selecting 200, 160, 80 or 40 readings from the original 240 fields. The mean PMN ratio, its 95% confidence interval (CI) and the coefficient of variation (CV) were calculated for each of the four levels of sampling. Both CI and CV increased as the number of readings decreased. Inflated lung tissue had consistently higher values for CV compared to non-inflated lung. In practice, we recommend that for both inflated and non-inflated lungs, 80-160 fields (approximate 0.23-0.45 mm2 of absolute area evaluated) need to be counted to yield a PMN ratio with acceptable accuracy and precision. The PMN ratio provides a simple and objective way of quantifying the degree of acute inflammation in clinical histopathology and experimental toxicology studies involving lungs. It is suitable for use in research of lung inflammation, and as an accessory diagnostic tool and an objective descriptor for clinical histopathology.

Diethylenetriamine Nitric Oxide Adduct Relaxes Precontracted Mouse Tracheal Smooth Muscle

1. Inhaled diethylenetriamine nitric oxide adduct (DETA/NO) has been shown to be a selective pulmonary vasodilator in animal and human studies. The aims of the present study were to investigate the effect of DETA/NO on mouse precontracted isolated tracheal smooth muscle preparations and to determine the active component of this compound.

Positive end-expiratory pressure adjusted for intra-abdominal pressure – A pilot study

Purpose: Intra‐abdominal hypertension (IAH) is associated with impaired respiratory function. Animal data suggest that positive end‐expiratory pressure (PEEP) levels adjusted to intra‐abdominal pressure (IAP) levels may counteract IAH‐induced respiratory dysfunction. In this pilot study, our aim was to assess whether PEEP adjusted for IAP can be applied safely in patients with IAH. Materials and methods: We included patients on mechanical ventilation and with IAH. Patients were excluded with severe cardiovascular dysfunction or severe hypoxemia or if the patient was in imminent danger of dying. Following a recruitment manoeuvre, the following PEEP levels were randomly applied: PEEP of 5 cmH2O (baseline), PEEP = 50% of IAP, and PEEP = 100% of IAP. After a 30 min equilibration period we measured arterial blood gases and cardio‐respiratory parameters. Results: Fifteen patients were enrolled. Six (41%) patients did not tolerate PEEP = 100% IAP due to hypoxemia, hypotension or endotracheal cuff leak. PaO2/FiO2 ratios were 234 (68), 271 (99), and 329 (107) respectively. The differences were significant (p = 0.009) only between baseline and PEEP = 100% IAP. Conclusions: PEEP = 100% of IAP was not well‐tolerated and only marginally improved oxygenation in ventilated patients with IAH. Highlights:Best positive end‐expiratory pressure (PEEP) to apply in patients with intra‐abdominal hypertension (IAH) is unknown.Applying PEEP adjusted for intra‐abdominal pressure to 100% improved oxygenation in some patients but was frequently not tolerated.Applying PEEP adjusted for intra‐abdominal pressure to 50% was well tolerated and improved respiratory compliance, but not oxygenation.