Table 5.

Investigations of systemic hydration induced voice changes in vivo employing pharmaceuticals

Ref	Patient	Hydration Inducement	Hydration Measures	Hydration Status	Vocal Function Measures	Main Results	Conclusions
Roh et al. (2006) (52)	20M 21–24 yr healthy	Method Avoid caffeine, alcohol, high sodium food, drugs, dehydrating substances, excessive eating or drinking of water, strenuous voice use Xerostomia intramuscular injection 0.3mg (1.5ml) glycopyrrolate Control intramuscular injection 1.5ml saline Timing Timing for general avoidance not specifically stated. Baseline, injections, post measure +3hrs	Method Saliva volume by modified swab Pt perception dry mouth (VAS) Timing Before & every 30mins for 3hrs post injection	Pre Not measured Post Not measured	Measures Acoustic Fo, jitter, shimmer NHR, voice range profiles Aerophone II max phonation time, average airflow, subglottal pressure PTP PPE - VAS post reading 20mins Lx imaging VAS vibratory closure pattern, supraglottic activity, presence of mucus, color, mucosal wave, amp & symmetry Timing Pre ✓ Post ✓	Saliva flow rates ↓ ~50% post glycopyrrolate injection post 30–60mins, lowest 90–120mins post injection Sig. ↑ dry mouth 30mins post highest level 120mins. ↑ PPE & PTP both groups post 3hrs, sig higher in treatment group. Voice range profile sig. ↓ pitch & loudness in treatment group No sig. change Max phonation time, average airflow, videostroboscopy ratings	Glycopyrrolate may induce decreases in mucosal wetness of VFs as well as oral mucosa. Salivary hypofunction may be closely related to vocal changes A change in vocal function should be considered for irradiated patients - current data is similar to previous investigation in head & neck cancer patients
Akhtar et al. (1999) (53)	8M 4F 27–55yr healthy	Method 250mg pure caffeine (5x Proplus tablets) Timing Post baseline measures	Method Caffeine (mg/l) blood Timing Pre & 1hr post ingestion	Pre Not measured Post Not measured	Measures Laryngograph Irregularity of Fo Free speech Reading passage ‘Happy Birthday’ Timing Pre ✓ Post ✓	Sig. effects btw patient, not within subjects (pre & post) in all 3 conditions Caffeine mg/l varied between patients Reading - substantial Fo variation in each task across patient prior to caffeine ingestion.	Considerable individual variability in response to caffeine ingestion Mean percentage of irregularity increased over time suggesting an effect on the VFs caused by caffeine ingestion
Erickson-Levendoski & Sivasankar (2011) (54)	8 M 8 F 18–27 yr 8 prior vocal training	Method Caffeine 2x coffees (~480mg) Control - 2x decaf coffee (~24mg) 70% humidity Timing 2 sessions at same time on 2 consecutive days 2nd coffee 2.3–3hrs post initial (left lab in between)	Method Not measured Timing Not measured	Pre Not measured Post Not measured	Measures PTP 10 80 PPE - VAS - ‘Happy Birthday’ 50% pitch range Measures taken post 35min & 70min vocal loading task Timing Pre ✓ Post ✓	No sig. effects of caffeine on PTP or PPE Ingestion of caffeine did not worsen the effects of vocal loading on PTP or PPE Vocal loading sig. ↑ PTP but not PPE	A high dose of caffeine does not adversely affect PTP or PPE measures
Ahmed et al. (2012) (58)	25 adults healthy	Method Caffeinated coffee ~400mg +routine water De-caffeinated coffee ~ 4–8mg +routine water Water only - ≤2l/day Additional carbonated drinks if same caffeine category but not permitted in water group No alcohol for any group Timing Ingestion of fluid for 2 days	Method Drink diary Timing 48h between measures	Pre Not measured Post Not measured	Measures Perceptual rating GRBAS Acoustics Fo, jitter, shimmer Timing Pre ✓ Post ✓	No statistical diff. in any measure of voice quality between groups pre- or post- intervention	Caffeinated coffee does not have a sig. detrimental effect on voice quality
Tanaka et al. (2001) (55)	4 M 26–35 yr healthy	Method Intravenous injection of atropine sulfate 0.5mg Timing 10mins prior to testing	Method Not measured Timing Not measured	Pre Not measured Post Not measured	Measures Change in frequency per unit change in transglottal pressure (dF/dP) Timing Pre ✓ Post ✓	Pt perceived dry throat post atropine No perceived hoarseness dF/dP ↓ at lower Fo but not higher Fo	Relationship between dF/DP & Fo reflects length-versus-depth adjustments for Fo control