Central venous-to-arterial carbon dioxide gradient as a marker of occult tissue hypoperfusion after major surgery.

The central venous-arterial carbon dioxide tension gradient ('CO2gap') has been shown to correlate with cardiac output and tissue perfusion in septic shock. Compared to central venous oxygen saturation (SCVO2), the CO2gap is less susceptible to the effect of hyperoxia and may be particularly useful as an adjunctive haemodynamic target in the perioperative period. This study investigated whether a high CO2gap was associated with an increased systemic oxygen extraction (O2ER >0.3) or occult tissue hypoperfusion in 201 patients in the immediate postoperative period. The median CO2gap of all patients was 8 mmHg (IQR 6 to 9), and a large CO2gap was very common (> 6mmHg in 139 patients [69%], 95% CI 63 to 75; >5 mmHg in 170 patients [85%], 95% CI 79 to 89). A CO2 gap >5 mmHg had a higher sensitivity (93%) and negative predictive value (74%) than a CO2gap >6 mmHg in excluding occult tissue hypoperfusion. Of the four variables that were predictive of an increased O2ER in the multivariate analysis-CO2gap, arterial pH, haemoglobin and arterial lactate concentrations-the CO2gap (odds ratio 4.41 per mmHg increment, 95% CI 1.7 to 11.2, P=0.002) was most important and explained about 34% of the variability in the risk of occult tissue hypoperfusion. In conclusion, a normal CO2 gap (<5 mmHg) had a high sensitivity and negative predictive value in excluding inadequate systemic oxygen delivery and may be useful as an adjunct to other haemodynamic targets in avoiding occult tissue hypoperfusion in the perioperative setting when high inspired oxygen concentrations are used.

A comparison of relative-frequency and threshold-hunting methods to determine stimulus intensity in transcranial magnetic stimulation.

OBJECTIVE: Stimulation intensity (SI) in transcranial magnetic stimulation is commonly set in relation to motor threshold (MT), or to achieve a motor-evoked potential (MEP) of predefined amplitude (usually 1 mV). Recently, IFCN recommended adaptive threshold-hunting over the previously endorsed relative-frequency method. We compared the Rossini-Rothwell (R-R) relative-frequency method to an adaptive threshold-hunting method based on parameter estimation by sequential testing (PEST) for determining MT and the SI to target a MEP amplitude of 1 mV (I(1) mV). METHODS: In 10 healthy controls we determined MT and I(1) mV with R-R and PEST using a blinded crossover design, and performed within-session serial PEST measurements of MT. RESULTS: There was no significant difference between methods for MT (52.6±2.6% vs. 53.7±3.1%; p=0.302; % maximum stimulator output; R-R vs. PEST, respectively) or I(1) mV (66.7±3.0% vs. 68.8±3.8%; p=0.146). There was strong correlation between R-R and PEST estimates for both MT and I(1) mV. R-R required significantly more stimuli than PEST. Serial measurements of MT with PEST were reproducible. CONCLUSIONS: PEST has the advantage of speed without sacrificing precision when compared to the R-R method, and is adaptable to other SI targets. SIGNIFICANCE: Our results in healthy controls add to increasing evidence in favour of adaptive threshold-hunting methods for determining SI.

Modulation of corticomotor excitability by an I-wave intervention delivered during low-level voluntary contraction.

Transcranial magnetic stimulation (TMS) interventions that modulate cortical plasticity may achieve a more functional benefit if combined with neuro-rehabilitation therapies. With a TMS protocol targeting I-wave dynamics, it is possible to deliver stimuli while a subject performs a motor task, and this may more effectively target functional networks related to the task. However, the efficacy of this intervention during a simple task such as a low-level voluntary contraction is not known. We delivered paired-pulse TMS at an inter-pulse interval (IPI) of 1.5 ms for 15 min while subjects performed a 10 ± 2.5% voluntary contraction of the first dorsal interosseous (FDI) muscle and made motor evoked potential (MEP) amplitude and short-interval intracortical facilitation (SICF) curve measurements. Pre-intervention SICF curves showed only a single peak at 1.3-1.5 ms IPI. During the intervention, MEP amplitude steadily increased (P < 0.001) to 137 ± 13% of its initial value. After the intervention, SICF curves were increased in amplitude (P < 0.001) and later peaks emerged at 2.8 and 4.3 ms IPIs. A control experiment, replacing paired-pulse stimulation with single-pulse stimulation showed no effect on MEP amplitude (P = 0.951). We conclude that the I-wave intervention can be administered concurrently with a simple motor task and that it acts by increasing trans-synaptic efficacy across a number of I-waves. The ability to perform a motor task simultaneously with a TMS intervention could confer a degree of specificity to the induced excitability changes and may be beneficial for functional neuro-rehabilitation programs built around motor learning and retraining.