It is, however, effective. I’m scared while playing Dead Space, though that feeling alternates with a droopy sense that I’m missing something, most likely the magic of 2008. I’m missing out on a PC to run those sooty, grainy graphics in someone’s dark dorm room. The reference value used for VR computation was 5.3 kPa 0.1 L min −1 kg −1, derived from patients during anaesthesia, 15 where 0.1 L min −1 kg −1 is assumed as the normal VE. To assess whether a similar reference value can be applied to critically ill patients, we selected among our 641 ICU patients 26 patients with ‘normal’ Pa co 2 and V D/V Tphys. The characteristics of this ARDS reference cohort are reported in Supplementary TableE1. The measured VE averaged 0.1 L min −1 kg PBW −1 and Pa co 2 averaged 5.3 kPa (0.4) – which were similar to those found in patients undergoing anaesthesia 5 , 15 and led to identical VR.

The association between VR and ICU mortality was examined through univariable and multivariable logistic regression models. To assess the association of VR with mortality when adjusted for covariates which could have a contribution to the VR, we performed a multivariable logistic regression including VCO 2, Pa O 2/FiO 2, and V D/V Tphys. To make an additional comparison of the ORs, we standardised all covariates by subtracting the mean and dividing by their sd. After standardisation, the ORs refer to a unit change in sd of each covariate – therefore giving all covariates numerically similar scales. Model coefficients are reported for standardised and non-standardised data. The aim of this multivariable analysis was not to find a model which included all the factors potentially associated to outcome (i.e. age, mechanical power), but to explore the effects of the physiological variables which contribute to the VR and its association to outcome once adjusted by these physiological confounders.

MAX FACTORY

Ventilatory ratio was associated with mortality, but non-ventilatory variables were the chief contributors to high ventilatory ratio values associated with severe illness.

where CaCO 2, CcCO 2, and CvcCO 2 are the CO 2 contents in arterial, pulmonary (ventilated) capillary, and mixed venous blood, respectively. Kuwabara and Duncalf 11 assumed that tensions and contents are in equilibrium and vary proportionately, and therefore the formula to correct dead space for shunt uses gas tensions instead of their contents. Although this assumption is not strictly accurate, using CO 2 contents or tensions provided similar results (see supplement). Therefore, despite its limitations, the Kuwabara equation is the bestavailable option to correct the dead space. The impact of Q va/Q on V D/V Tphys may be relevant at Q va/Q>0.2–0.3 ( Supplementary Fig.E1, panel A). Indeed, the ‘physiological’ dead space in pathological conditions represents the entirety of the gas exchange dysfunction, as it is influenced both by wasted ventilation (dead space ventilation) and wasted perfusion (Q va/Q). There are options for how you’d like to accomplish this. Maybe you prefer the Plasma Cutter, Pulse Rifle, or the Ripper, which shoots saw blades. I’ve become attached to the Force Gun, a Dead Space 2 acquisition, which uses the game’s gravity manipulation module, Kinesis, to blast away necromorphs until they become piles of rattled bones. The main results of this study are: (1) the effect of Q va/Q on absolute VR becomes larger with increasing V D/V Tphys; (2) the effect of VCO 2 is also of major significance, particularly when VR is corrected for Q va/Q; (3) VR is a useful aggregate variable associated with outcome; however, it does not only reflect V D/V Tphys but also important contributions from VCO 2 ( Fig 1) and Q va/Q, reflected by Pa O 2/FiO 2 ( Supplementary FigureE2). These data suggest that VCO 2 and Q va/Q contribute to the high values of VR seen in the most severe categories of patients. VR correlates strongly with V D/V Tphys, 5 does not require measurement of mixed expired CO 2, and can be easily calculated from a few routinely collected variables. 6 In addition, the unitless VR is easy to interpret, as it is normalised to a predefined ‘standard’ and quantifies the degree of impaired CO 2 elimination in relation to an expected reference value. However, VR may be affected by factors such as venous admixture (Q va/Q) and CO 2 volume expired per minute (VCO 2), which can alter the absolute value of VR despite an unchanged dead space ventilation. The potential effects of these two factors on VR, in particular Q va/Q, have been described but not quantified. 7 Specifically, there are no clinical data that establish the relative importance of measured Q va/Q on VR, nor the relative importance of VCO 2 on VR when the V D/V Tphys is adjusted for the degree of Q va/Q. These considerations are particularly important in patients with more severe disease, in whom the assumption that virtually all of the variations in VR are attributable to an increased V D/V Tphys 8 may be confounded by the effect of larger venous admixture. Sinha and colleagues 7 found weak and non-significant association between VCO 2 and VR. They attributed this to the smaller and short-lived variation in VCO 2 compared with the larger variations of V D/V Tphys. However, we found that the effects of VCO 2 are more marked when VR is corrected for Q va/Q. The recognition that venous admixture (Q va/Q) and VCO 2 can change the absolute value of VR despite an unchanged dead space ventilation has several potential implications: (1) Changes in VR may not be attributed to a change in V D/V T if there are associated variations in oxygenation or VCO 2. This may affect the interpretation of the effect of therapeutic manoeuvres such as prone position, PEEP selection, or pulmonary vasodilators on the change in V D/V T. In these examples, changes in VR may be determined by a variable combination of reduction in Q va/Q and V D/V T– but not necessarily exclusively in V D/V T. (2) In patients with more severe disease, the variations in VR may be confounded by the effect of larger Q va/Q. In this case, interventions that affect Q va/Q may disproportionally affect VR and affect the assumption of the underlying pathophysiological mechanisms. (3) Prediction models using VR as a proxy of V D/V T can inflate the range and its prognostic effect. (4) Although VCO 2 disparities may appear a minor problem in general cohort, the VR dependency on this variable makes its use misleading in cases of abnormal VCO 2 or during extracorporeal support, where a substantial portion of CO 2 may be cleared by the membrane lung. In that setting, V D/V Tphys fully reflects the lung status, whereas VR may appear normal or even low.As for Dead Space, a debut at No.2 means that it has had a much better start in life than last year’s The Callisto Protocol. Widely considered a spiritual successor to Dead Space thanks to being helmed by the original game’s co-creator Glenn Schofield, some may have expected The Callisto Protocol to have made something of a splash. But despite that pedigree, it debuted at an underwhelming No.17 in the NPD sales charts for December 2022. The major limitation of this work, beyond its retrospective design, is that VCO 2 was estimated rather than measured. The computation relies on the Harris–Benedict equation, which estimates the ‘standard’ VCO 2 production based on age, height, and weight (Supplementary material, equation [19]). In ICU patients, we may expect remarkable discrepancies between the actual and the predicted VCO 2. Yet, in the 176 patients in which VCO 2 was measured, the relationship with the computed VCO 2 was acceptable and the bias between measured and computed VCO 2 was –22 (48) ml, despite the large variability of their absolute values ( Supplementary Fig.E4). Any inaccuracy of VCO 2 estimation should affect the V D/V T (Supplementary material, Equation [2]), whereas it would not affect the calculation of VR. The measured and estimated V D/V Tphys values computed in 176 individuals, however, were similar (0.65 [0.13] and 0.59 [0.12], respectively). In the entire cohort, V D/V Tphys, Pa O 2/FiO 2, and VR were independently associated with mortality. The OR for mortality of VR and V D/V Tphys were respectively 2.5 (95% CI, 1.8–3.5) and 7.04 (95% CI, 1.9–27.7). The area under the receiver operating characteristic (ROC) curve was 0.64 (95% CI, 0.59–0.68) for VR and 0.66 (95% CI, 0.62–0.71) for V D/V Tphys. When the effect of VR on mortality was adjusted – in a multivariable model – for variables proven to affect VR in the physiological modelling (i.e. V D/V Tphys, VCO 2, Pa O 2/FiO 2), VR was no longer independently associated with mortality, OR adj=1.2 (95% CI, 0.7–2.1).