Merging PRK and Collagen Crosslinking: An Analysis of Literature and a Guide to Prevalent Protocols.

PURPOSE: The purpose of this review was to summarize the different surgical approaches combining photorefractive keratectomy (PRK) and corneal crosslinking (CXL), present each protocol template in a simple format, and provide an overview of the primary outcomes and adverse events. METHODS: A literature review was conducted as outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Eight different databases were searched. Papers were included if PRK was immediately followed by CXL. RESULTS: Thirty-seven papers met the inclusion criteria of a total yield of 823. The latest research into simultaneous PRK and CXL has been shown to not only stabilize the cornea and prevent keratoconus progression but also improve the visual acuity of the patient. Improvements in uncorrected distance visual acuity and (spectacle) corrected distance visual acuity were found to be significant when considering all protocols. There were also significant reductions in K1, K2, mean K, Kmax, sphere, cylinder, and spherical equivalent. Random-effects analysis confirmed these trends. Corrected distance visual acuity was found to improve by an average of 0.18 ± 1.49 logMAR (Cohen's D [CD] 0.12; P <0.02). There was also a significant reduction of 2.57 ± 0.45 D (CD 5.74; P <0.001) in Kmax. Cylinder and spherical equivalent were also reduced by 1.36 ± 0.26 D (CD 5.25; P <0.001) and 2.61 ± 0.38 D (CD 6.73; P <0.001), respectively. CONCLUSIONS: Combining the 2 procedures appears to be of net benefit, showing stabilization and improvement of ectatic disease, while also providing modest gains in visual acuity. Since customized PRK and CXL approaches appear superior, a combination of these would likely be best for patients.

Five-Year Incidence, Management, and Visual Outcomes of Diffuse Lamellar Keratitis after Femtosecond-Assisted LASIK.

Femtosecond (FS) lasers initially had a higher incidence of diffuse lamellar keratitis (DLK) compared with microkeratome flap creation. It has been theorized that higher-frequency lower-energy (HFLE) FS lasers would reduce the incidence of DLK. Our study sought to evaluate the incidence of newer HFLE FS lasers with pulse frequencies above 60 kHz. It was a retrospective case-control study evaluating the incidence of DLK following flap creation with one of three FS lasers (AMO iFs, WaveLight FS200, Zeiss VisuMax). Uncomplicated LASIK cases were included as the control group (14,348 eyes) and cases of DLK were recorded in the study group (637 eyes). Of the 637 cases of DLK, 76 developed stage II, 25 progressed to stage III, and only three developed stage IV DLK. The overall incidence rate of DLK was 4.3%; it has fallen with the invention of newer HFLE FS lasers and is approaching the DLK incidence rates of DLK with microkeratome.

Onconase, an anti-tumor ribonuclease suppresses intracellular oxidative stress.

Onconase (ONC), an antitumor ribonuclease from oocytes of a frog Rana pipiens, capable of inducing apoptosis in many cell lines is synergistic with several other anticancer drugs. Since cytotoxic effects of numerous drugs are modulated by reactive oxygen intermediates (ROI), we have studied effects of ONC on the intracellular level of oxidants in several normal cell types as well as tumor cell lines. It is demonstrated for the first time that ONC substantially decreases the content of ROI in all cell lines studied. This effect depends on the ribonucleolytic activity of the enzyme and is due to both, decreased rate of ROI generation and accelerated rate of their degradation. Onconase decreases the mitochondrial transmembrane potential and consequently, generation of ATP. Simultaneously the enzyme decreases the expression of an antiapoptotic protein Bcl-2, and upregulates the proapoptotic Bax protein. These finding are consistent with the enzyme propensity to induce apoptosis. The observed antioxidant activity of ONC may be an important element of its cytotoxicity towards cancer cells. The enzyme seems to exert its biological activities by interfering with the redox system of cellular regulation.

Remifentanil pharmacokinetics in obese versus lean patients.

BACKGROUND: Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics. METHODS: Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed. RESULTS: The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations. CONCLUSIONS: The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.

Intracranial pressure, middle cerebral artery flow velocity, and plasma inorganic fluoride concentrations in neurosurgical patients receiving sevoflurane or isoflurane.

UNLABELLED: This study examined the concentration-related effects of sevoflurane and isoflurane on cerebral physiology and plasma inorganic fluoride concentrations. Middle cerebral artery flow velocity (Vmca), intracranial pressure (ICP), electroencephalogram (EEG) activity, and jugular bulb venous oxygen saturation were measured, and cerebral perfusion pressure (CPP) and estimated cerebral vascular resistance (CVRe) were calculated at baseline and at 0.5, 1.0, and 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane (n = 8) or isoflurane (n = 6). Mannitol 0.5-0.75 g/kg was given before dural incision, and blood was sampled for plasma inorganic fluoride during surgery and for up to 72 h postoperatively. Both sevoflurane and isoflurane decreased Vmca (to 31 +/- 12 - 36 +/- 14 cm/s, mean +/- SD), did not significantly alter ICP (13 +/- 9 - 15 +/- 11 mm Hg), and did not cause epileptiform EEG activity. With sevoflurane, decreased Vmca was accompanied by decreased CPP and unchanged CVRe at 0.5 MAC, and unchanged CPP and increased CVRe at 1.0 and 1.5 MAC. Plasma inorganic fluoride was 39.0 +/- 12.9 microM at the end of anesthesia (3.2 +/- 2.0 MAC hours) with sevoflurane, similar to the value (36.2 +/- 3.9 microM) for 3.7 +/- 0.1 MAC hours sevoflurane in patients not receiving mannitol. Decreased Vmca during sevoflurane presumably results from decreased cerebral metabolic rate, with CVRe changing secondarily in accord with CPP. Plasma inorganic fluoride does not seem to be altered by mannitol-induced diuresis. IMPLICATIONS: In neurosurgical patients, sevoflurane decreased middle cerebral artery flow velocity and caused no epileptiform electroencephalogram activity and no increase of intracranial pressure or plasma inorganic fluoride. These effects are suitable for neurosurgery. Two other possible effects of sevoflurane, i.e., increased cerebrospinal fluid volume and/or intracranial elastance, may not be suitable for neurosurgery and warrant further study.

Reduction of antiarrhythmic drug use in patients receiving implantable cardioverter defibrillators.

Widespread use of implantable cardioverter defibrillators (ICDs) for the treatment of ventricular tachycardia (VT) and ventricular fibrillation (VF) occurred in the late 1980s and early 1990s. Additionally, there has been increasing appreciation during this time for both the lack of efficacy and proarrhythmic activity of antiarrhythmic drugs to treat these cardiac arrhythmias. We evaluated the use of antiarrhythmic drugs from 1987 to 1991 (5-year period) at the time of ICD implantation in 25,450 patients. The use of all classes of antiarrhythmic agents decreased from 61% to 24% during this time period (P < 0.05). In addition, there was a significant reduction in antiarrhythmic agent use for each drug class (P < 0.05) with the exception of Class II agents (beta blockers). These changes in drug use occurred independent of any changes in age, sex, ejection fraction, prevalence of coronary artery disease, or type of ventricular arrhythmia (VT vs VF).

Radiofrequency catheter ablation of sinus node reentrant tachycardia.

Sinus node reentrant tachycardia is a relatively uncommon (5%-15%) form of recurrent paroxysmal supraventricular tachycardia (SVT). We describe a case of symptomatic sinus node reentrant tachycardia in a 67-year-old male with ischemic heart disease, congestive heart failure, and depressed ventricular function. Adenosine administered during an electrophysiology study caused prolongation of the tachycardia cycle length due to atrial cycle length prolongation (without atrio-His prolongation) prior to tachycardia termination. Right atrial mapping revealed the earliest site of atrial activation in the high lateral right atrium just below the superior vena cava. Low energy (10 and 20 W) radiofrequency lesions were applied at this site with termination of the tachycardia within 3 seconds of radiofrequency energy delivery. Tachycardia could not be reinduced after delivery of the radiofrequency lesions. The sinus node function immediately and 6 weeks after radiofrequency catheter ablation remained normal and the patient was without clinical recurrence of SVT. Mapping of sinus node reentrant tachycardia and elimination of the reentrant circuit with radiofrequency catheter ablation is possible without causing sinus node dysfunction. Adenosine causes prolongation of the atrial cycle length followed by termination of sinus node reentrant tachycardia.

Endotracheal tube cuff pressure increases significantly during anterior cervical fusion with the Caspar instrumentation system.

To determine whether endotracheal tube cuff pressure increases significantly with surgical retraction and cervical spine distraction during anterior cervical spine surgery with Caspar instrumentation, we prospectively studied 10 patients undergoing this procedure. The tracheas of all patients were intubated with a Mallinckrodt Hi-Lo endotracheal tube. Tracheal tube cuff pressures measured with a transducer system were 42.4 mm Hg +/- 7.0 mm Hg (SEM) after intubation and cuff inflation. Air was removed from the endotracheal tube cuff until the trachea was just barely sealed at a cuff pressure of 15.2 mm Hg +/- 1.6 mm Hg. The endotracheal tube cuff pressure was readjusted to "just-seal" pressure before the surgeons introduced the Caspar instrumentation. The cuff pressure with traction and distraction was 43.2 mm Hg +/- 5.0 mm Hg. This pressure was significantly increased from the "just-seal" pressure, and from the cuff pressure after instrumentation was discontinued (9.8 mm Hg +/- 2.3 mm Hg). We conclude that anterior cervical spine surgery with Caspar instrumentation is associated with a significant increase in endotracheal tube cuff pressure.

Doppler echocardiographic assessment of an impedance-based dual-chamber rate-responsive pacemaker.

Rate-responsive pacing allows patients with chronotropic incompetence to achieve more physiologic heart rate responses to exercise. One sensor currently being investigated uses impedance-derived measurements of changes in right ventricular stroke volume to alter the pacing rate. Correlation of pacemaker-derived measurements of stroke volume with an accepted method of stroke volume measurement has not been performed. The relative changes in impedance-derived stroke volume were compared in 10 patients with an impedance-based dual-chamber rate-responsive pacemaker (Precept DR, Cardiac Pacemakers, Inc.) with simultaneous Doppler echocardiographic measurements of right and left ventricular stroke volume. These comparisons were made during pacing at 2 heart rates (70 and 100 beats/min) and 3 AV intervals (150, 200 and 250 ms) while in a supine resting state, during lower body negative pressure to -30 mm Hg, and while performing 25% maximal handgrip. Pacemaker-derived stroke volume decreased by 7 to 11% and Doppler time-velocity integral measurements decreased by 14 to 19% in response to an increase in pacing rate (p = NS). There was also no significant difference by either technique in the mean stroke volume change when the atrioventricular interval was varied. Both techniques detected a decrease in stroke volume during lower body negative pressure, ranging from -7 to -20% by pacemaker, and -17 to -38% by Doppler. Overall, the pacemaker stroke volume measurements responded in an appropriate direction to each intervention, signaling the pacemaker's ability to detect directional change in stroke volume. The Precept DR may aid in the programming of parameters such as atrioventricular interval and heart rate by allowing for optimization of stroke volume in individual patients.

The influence of hemorrhage on organ perfusion during deliberate hypotension in rats.

There is general concern that major blood loss during deliberate hypotension could produce severe organ ischemia, but documentation of the magnitude of this response remains obscure. To examine this response, we studied 43 male Sprague-Dawley rats that were divided into seven groups: the control animals received 1 MAC (1.4%) isoflurane only; the hypotensive animals received a 1.4% isoflurane baseline anesthetic and were then rendered hypotensive by either increasing the isoflurane concentration (dISO), or by adding sodium nitroprusside (SNP), or 2-chloroadenosine (2AD) to the baseline anesthetic, decreasing the MAP to 51 mmHg; hemorrhaged animals had hypotension produced in the same manner as for the hypotensive animals, but additionally were bled 20% of estimated blood volume during deliberate hypotension produced with either deep isoflurane (dISOH), sodium nitroprusside (SNPH), or 2-chloroadenosine (2ADH). After a 25-min period of hypotension, or hypotension plus hemorrhage, cardiac output and blood flow to brain, heart, gastrointestinal tract, kidney, and liver were measured with 141Ce-labelled 15-microns microspheres. Hypotension was associated with decreased blood flow to the kidneys in all groups and to the liver in the 2AD group and an increased blood flow to the heart in the SNP and 2AD groups. Hemorrhage decreased blood flow during deliberate hypotension to the brain and the gastrointestinal tract in the dISOH and 2ADH groups and to the liver in the dISOH group. Our results suggest that hemorrhage during deliberate hypotension with dISO or isoflurane plus 2AD may be associated with compromised organ blood flow, whereas blood flow to vital organs is maintained after 20% hemorrhage during isoflurane and superimposed SNP-induced hypotension.

Fentanyl and sufentanil increase intracranial pressure in head trauma patients.

Although opioids frequently are administered to patients with severe head trauma, the effects of such drugs on intracranial pressure are controversial. Nine patients with severe head trauma were studied for the effects of fentanyl and sufentanil on intracranial pressure (ICP). In all patients, ICP monitoring was instituted before the study. Full neuromuscular blockade was achieved with vecuronium bromide before the administration of either fentanyl (3 micrograms.kg-1) or sufentanil (0.6 microgram.kg-1) as an intravenous bolus over a 1-min period in a masked and random fashion. Patients received the other opioid in the same fashion 24 h later. Arterial blood pressure, heart rate, and ICP were recorded continuously for the 1 h after drug administration. Fentanyl was associated with an average ICP increase of 8 +/- 2 mmHg, and sufentanil with an increase of 6 +/- 1 mmHg. These increases were statistically significant. Both drugs produced clinically mild decreases in mean arterial blood pressure (fentanyl, 11 +/- 6 mmHg; sufentanil, 10 +/- 5 mmHg) that nevertheless were statistically significant. No significant changes in heart rate occurred. These results indicate that modest doses of potent opioids can significantly increase ICP in patients with severe head trauma.